Name: 672-89-9|4-Methoxy-6-methyl-2H-pyran-2-one|98%
Brand: Ambeed
SKU: A223119
Rating: 99 (30 reviews)

1
[ 675-10-5 ]
[ 77-78-1 ]
[ 672-89-9 ]

Yield	Reaction Conditions	Operation in experiment
96%	With sodium carbonate In acetone Heating;
91%	With potassium carbonate In acetone at 20℃;	Synthesis of 4-methoxy-6-methyl-2-pyrone (compound 2): 4-hydroxy-6-methyl-2-pyrone (11.2 mmol), potassium carbonate (33.6 mmol), acetone (20 mL), dimethyl sulfate (22.4 mmol), overnight at room temperature. The reaction was checked by TLC. After the reaction was completed, the solvent was removed under reduced pressure. The mobile phase was cyclohexane:ethyl acetate (v/v) 1:4. Compound 2 was obtained; yield: 91%.
89%	With potassium carbonate In butanone for 20h; Reflux;	4-Methoxy-6-methyl-2H-pyran-2-one (3). A 200-mL flask was charged with 4-hydroxy-6-methyl-2H-pyran-2-one (3.78 g, 30 mmol), dimethyl sulfate (3.78 g,30 mmol), K2CO3 (10 g), and butan-2-one (50 mL), and the mixture was refluxed for 20 h. The mixturewas cooled and filtered, and the filtrate was evaporatedunder reduced pressure in a rotary evaporator. Theproduct was recrystallized from petroleum ether. Yield89 %, yellow solid, mp 86°C [26]. IR spectrum, ν, cm-1:1732, 1720 (C=O), 1649 (C=C), 1464, 1401, 1148(C-O-C), 943, 545. 1 NMR spectrum, δ, ppm: 2.21 s(3H, CH3), 3.81 s (3H, CH3O), 5.40 d (1H, 3-H), 5.79d (1H, 5-H). 13 NMR spectrum, δC, ppm: 19.7, 55.7,87.2, 100.2, 161.8, 164.9, 171.2. Mass spectrum, m/z(Irel, %): 140 (53) [M]+, 132 (8.6), 125 (47), 113 (8),112 (100), 69 (36), 59 (25), 53 (30), 43 (45). C7H8O3.M 140.15.

86%	With potassium carbonate In dimethyl sulfoxide at 20℃; for 1h;
85%	With sodium carbonate In acetone for 12h; Heating;
85%	With potassium carbonate In acetone at 20℃;
85%	With potassium carbonate In acetone at 20℃;	3.1.1 4-methoxy-6-methyl-2H-pyran-2-one (2) A mixture of 4-hydroxy-6-methyl-2H-pyran-2-one (2.60mmol) and K2CO3 (2.60mmol) and (CH3)2SO4 (2.60mmol) in acetone (15mL) was stirred at room temperature overnight. The mixture was filtered. The filtrate was concentrated in vacuum. The residue was purified with silica gel chromatography using chloroform as eluent to obtain target compound 2 as white solid. Yield: 86%; 1H NMR (400MHz, CDCl3) δ 5.71 (s, 1H), 5.34 (s, 1H), 3.73 (s, 3H), 2.14 (s, 3H).
84%	With potassium carbonate In acetone at 20℃; for 16h; Inert atmosphere;
84%	With potassium carbonate In acetone at 20℃;	1 Example 1 4-Methoxy-6-methyl2H-pyrone (Compound 2) 62.4g K2CO3with9.8 mL Me2SO4 was added to the dish200mLAnhydrous acetone inside the flask,And then add 10g in batches4-hydroxy-6-methyl-2H-pyrone (numberedCompound 1),Stir overnight at room temperature.filter,The solid was washed with acetone,The filtrate was distilled under reduced pressure,The resulting crude product was purified by column chromatography to give 9.3 g of a white solid,The white solid is 4-methoxyYl-6-methyl-2H-pyrone (numbered Compound 2) in 84% yield
82%	Stage #1: 4-hydroxy-6-methyl-2-pyron With potassium carbonate In dimethyl sulfoxide at 20℃; for 0.333333h; Inert atmosphere; Stage #2: dimethyl sulfate In dimethyl sulfoxide at 20℃; for 2h; Inert atmosphere;	General Procedure for the synthesis of alkyl substituted 4-Methoxy-2-pyrone segments General procedure: To a mixture of pyrone (1.0 equiv.) and potassium carbonate (2.0 equiv.) in DMSO (10 mL) was added at room temperature and stirred for 20 min, dimethyl sulfate (2.0 equiv.) was added and continued stirring at the same temperature for 2 h under nitrogen atmosphere. The mixture was poured into water and extracted with EtOAc. The combined organic extract was washed with water, brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel (100-200 mesh) column chromatography, eluted with 10 % acetone in dichloromethane to afford the O-methylated pyrone.
80%	With potassium carbonate In acetone Inert atmosphere; Reflux;
79%	Stage #1: 4-hydroxy-6-methyl-2-pyron; dimethyl sulfate With potassium carbonate In butanone at 90℃; Stage #2: for 20h; Reflux;	4-Methoxy-6-methyl-2H-pyran-2-one (III) A 200 mL flask was loaded by 4-hydroxy-6-methyl-2H-pyran-2-one (20 mmol, 2.52 g), dimethyl sulfate (20 mmol, 2.52 g), K2CO3 (8 g), and butan-2-one (40 mL) and stirred at 90°C. Upon cooling down the reaction mixture was filtered and the solvent evaporated under reduced pressure in a rotary evaporator. The residue was refluxed for 20 h. The product was recrystallized from petroleum ether.
76%	With potassium carbonate In acetone for 3h; Heating / reflux;	5 Potassium carbonate (71.2 g, 515 mmol) and dimethylsulfate (48.7 mL, 515 mmol) was added to a solution of compound J (50.0 g, 396 mmol) in dry acetone (1.45 L). The mixture was heated to reflux for 3 hours and cooled to room temperature. The solids were removed by filtration and the filtrate was concentrated. The oily residue was purified by silica gel chromatography (ethyl acetate : hexane = 1 :1) to give an oily solid. The oily solid was washed with diisopropylether to afford compound K (42.3 g, 76%) as a yellow powder. 1H NMR (CDCI3, 400MHz) : δ 2.21 (3H, s), 3.79 (3H, s), 5.41 (IH, d, J = 1.8 Hz), 5.77-5.78 (IH, m). EIMS (+) : 140 [M]+
	With sodium hydroxide
	With potassium carbonate In 2-methoxy-ethanol
	With potassium carbonate In butanone
	With potassium carbonate In dimethyl sulfoxide at 20℃;
	With potassium carbonate In acetone for 12h;	S1.16. Synthesis of 1e To a solution of 4-hydroxy-6-methyl-pyrone (5 g, 39.6 mmol) in acetone (230 mL), K2CO3 (6.58 g, 47.6 mmol) and (CH3)2SO4 (6 g, 47.6 mmol) were added, and the reaction mixture stirred for 12 hr. After concentration under reduced pressure, resultant mixture was extracted with EtOAc. Reaction product was purified on silica gel open column chromatography (hexane:EtOAc = 2:1) and obtained (1e, 4.9 g, 35.0 mmol). The NMR data were identical with that of previous report.

Reference： [1]Effenberger, Franz; Schoenwaelder, Karl-Heinz [Chemische Berichte, 1984, vol. 117, # 11, p. 3270 - 3279]
[2]Current Patent Assignee: SUN YAT-SEN UNIVERSITY (CHINA) - CN107793353, 2018, A Location in patent: Paragraph 0039; 0043
[3]Benferrah; Hammadi; Berthiol [Russian Journal of General Chemistry, 2016, vol. 86, # 12, p. 2881 - 2886][Zh. Obshch. Khim., 2016]
[4]Fang, Zhanxiong; Liao, Pei-Chun; Yang, Yu-Liang; Yang, Feng-Ling; Chen, Yi-Lin; Lam, Yulin; Hua, Kuo-Feng; Wu, Shih-Hsiung [Journal of Medicinal Chemistry, 2010, vol. 53, # 22, p. 7967 - 7978]
[5]Hansen, Chad A.; Frost [Journal of the American Chemical Society, 2002, vol. 124, # 21, p. 5926 - 5927]
[6]Cheng, Bao; Lin, Yongsheng; Kuang, Ming; Fang, Sai; Gu, Qiong; Xu, Jun; Wang, Laiyou [Chemical Biology and Drug Design, 2015, vol. 86, # 5, p. 1121 - 1130]
[7]Li, Chanjuan; Cheng, Bao; Fang, Sai; Zhou, Huihao; Gu, Qiong; Xu, Jun [European Journal of Medicinal Chemistry, 2018, vol. 143, p. 114 - 122]
[8]Fang, Sai; Chen, Lei; Yu, Miao; Cheng, Bao; Lin, Yongsheng; Morris-Natschke, Susan L.; Lee, Kuo-Hsiung; Gu, Qiong; Xu, Jun [Organic and Biomolecular Chemistry, 2015, vol. 13, # 16, p. 4714 - 4726]
[9]Current Patent Assignee: SUN YAT-SEN UNIVERSITY (CHINA) - CN104592182, 2017, B Location in patent: Paragraph 0028; 0029
[10]Basu, Manas K.; Mukkanti, K.; Samala, Ramakrishna [Tetrahedron Letters, 2022, vol. 88]
[11]Location in patent: experimental part Soldi, Cristian; Moro, Angelica V.; Pizzolatti, Moacir G.; Correia, Carlos R. D. [European Journal of Organic Chemistry, 2012, # 19, p. 3607 - 3616]
[12]Benferrah; Hammadi; Berthiol [Russian Journal of General Chemistry, 2015, vol. 85, # 8, p. 1939 - 1944][Zh. Obshch. Khim., 2015, vol. 85, # 8, p. 1939 - 1944,6]
[13]Current Patent Assignee: KYORIN HOLDINGS, INC. - WO2008/36379, 2008, A2 Location in patent: Page/Page column 60-61
[14]Janiszewska-Drabarek [Roczniki Chemii, 1953, vol. 27, p. 456,464][Chem.Abstr., 1955, p. 3176]
[15]Sib,S. [Tetrahedron, 1975, vol. 31, p. 2229 - 2235]
[16]March, P. de; Moreno-Manas, M.; Pleixats, R.; Ripoll, I. [Heterocycles, 1984, vol. 21, # 2, p. 766]
[17]Kumagai, Momochika; Nishikawa, Keisuke; Mishima, Takashi; Yoshida, Izumi; Ide, Masahiro; Koizumi, Keiko; Nakamura, Munetomo; Morimoto, Yoshiki [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 11, p. 2401 - 2406]
[18]Matsumoto, Takahiro; Kitagawa, Takahiro; Imahori, Daisuke; Matsuzaki, Atsushi; Saito, Youhei; Ohta, Tomoe; Yoshida, Tatsusada; Nakayama, Yuji; Ashihara, Eishi; Watanabe, Tetsushi [Bioorganic and Medicinal Chemistry Letters, 2021, vol. 45]

2
[ 672-89-9 ]
[ 670-35-9 ]

Yield	Reaction Conditions	Operation in experiment
89%	With N-Bromosuccinimide In tetrachloromethane at 80℃; for 1h;
88%	With N-Bromosuccinimide In tetrachloromethane for 1h; Heating;
86%	With N-Bromosuccinimide; Perbenzoic acid In tetrachloromethane for 17h; Heating;

83%	With N-Bromosuccinimide; Perbenzoic acid In tetrachloromethane for 7h; Heating; Irradiation; other concentration of substrate, other reaction time, without irradiation;
74%	With bromine In dichloromethane for 0.5h; Ambient temperature;
46%	With N-Bromosuccinimide; iodine In tetrachloromethane for 2h; Heating;
	With tetrachloromethane; N-Bromosuccinimide

Reference： [1]Schieferdecker, Sebastian; Shabuer, Gulimila; Knuepfer, Uwe; Hertweck, Christian [Organic and Biomolecular Chemistry, 2019, vol. 17, # 25, p. 6119 - 6121]
[2]Lokot; Pashkovskii; Lakhvich [Russian Journal of Organic Chemistry, 1998, vol. 34, # 9, p. 1350 - 1354]
[3]Bacardit, R.; Moreno-Manas, M.; Pleixats, R. [Journal of Heterocyclic Chemistry, 1982, vol. 19, p. 157 - 160]
[4]Bacardit, R.; Moreno-Manas, M.; Pleixats, R. [Journal of Heterocyclic Chemistry, 1982, vol. 19, p. 157 - 160]
[5]March, P. de; Moreno-Manas, M.; Pi, R.; Ripoll, I.; Sanchez-Fernando, F. [Journal of Heterocyclic Chemistry, 1985, vol. 22, p. 1537 - 1542]
[6]Poulton; Cyr [Canadian Journal of Chemistry, 1982, vol. 60, # 22, p. 2821 - 2829]
[7]Harris et al. [Journal of Organic Chemistry, 1970, vol. 35, p. 1329]

3
[ 672-89-9 ]
[ 75-77-4 ]
[ 77037-53-7 ]

Yield	Reaction Conditions	Operation in experiment
92%	Stage #1: 4-methoxy-6-methyl-2H-pyran-2-one With methyllithium In tetrahydrofuran at -120℃; Stage #2: chloro-trimethyl-silane In tetrahydrofuran at -78℃;
45%	With n-butyllithium at -78℃;

Reference： [1]Younis, Younis M.; Al-Shihry, Shar S. [Australian Journal of Chemistry, 2000, vol. 53, # 7, p. 589 - 591]
[2]Carpenter, T. Adrian; Jenner, Peter J.; Leeper, Finian J.; Staunton, James [Journal of the Chemical Society. Chemical communications, 1980, # 24, p. 1227]

4
[ 672-89-9 ]
[ 29736-80-9 ]
[ 77269-98-8 ]

Reference： [1]Journal of Organic Chemistry,1981,vol. 46,p. 2566 - 2570

5
[ 672-89-9 ]
[ 4885-02-3 ]
[ 84016-84-2 ]

Yield	Reaction Conditions	Operation in experiment
57%	With titanium tetrachloride In dichloromethane at 0 - 20℃; for 6h;
37%	With hydrogenchloride; titanium tetrachloride In chloroform at 20℃; for 19h;

Reference： [1]Oikawa, Hideaki; Kobayashi, Tomonori; Katayama, Kinya; Suzuki, Yuichi; Ichihara, Akitami [Journal of Organic Chemistry, 1998, vol. 63, # 24, p. 8748 - 8756]
[2]Poulton; Cyr [Canadian Journal of Chemistry, 1982, vol. 60, # 22, p. 2821 - 2829]

6
[ 672-89-9 ]
[ 922-67-8 ]
[ 35598-05-1 ]
[ 108593-44-8 ]

Reference： [1]Chemische Berichte,1987,vol. 120,p. 1339 - 1346

7
[ 672-89-9 ]
[ 762-42-5 ]
[ 108298-35-7 ]

Yield	Reaction Conditions	Operation in experiment
90%	at 200℃; for 2h;
89%	at 180 - 200℃;
76%	at 180 - 210℃; for 1.5h;	5 A mixture of compound K (41.4 g, 295 mmol) and dimethyl but-2-ynedioate (47.2 mL, 384 mmol) was stirred at 180 0C for 1 hour, then at 210 0C for 30 minutes. The mixture was cooled to room temperature and purified by silica gel chromatography (ethyl aceate : hexane = 20 : 1 - 4 : 1 ) to give compound L (53.4 g, 76%) as a pale-yellow oil. 1H NMR (CDCl3, 400MHz) : δ 2.34 (3H, s), 3.84 (3H, s), 3.88 (3H, s), 3.90 (3H, s), 6.91 (IH, d, J - 2.4 Hz), 7.29 (IH, d, J = 2.4 Hz). EIMS (+) : 238 [M]+

73%	In neat (no solvent) at 180 - 210℃; for 3h;
66%	1.) 180 deg C, 1 h, 2.) 210 deg C, 2 h;
35%	With benzophenone In acetone at -20 - -10℃; for 5h; Irradiation;

Reference： [1]Ziegler, Thomas; Layh, Marcus; Effenberger, Franz [Chemische Berichte, 1987, vol. 120, p. 1347 - 1356]
[2]Watanabe; Furuuchi; Yamaguchi; Kitahara [Organic letters, 1999, vol. 1, # 7, p. 1079 - 1080]
[3]Current Patent Assignee: KYORIN HOLDINGS, INC. - WO2008/36379, 2008, A2 Location in patent: Page/Page column 60-61
[4]Huang, Jing-Kai; Yang Lauderdale, Tsai-Ling; Shia, Kak-Shan [Organic Letters, 2015, vol. 17, # 17, p. 4248 - 4251]
[5]Tam, Tim Fat; Coles, Peter [Synthesis, 1988, # 5, p. 383 - 386]
[6]Somekawa, Kenichi; Shimo, Tetsuro; Yoshimura, Hiroyuki; Suishu, Takaaki [Bulletin of the Chemical Society of Japan, 1990, vol. 63, # 12, p. 3456 - 3461]

8
[ 672-89-9 ]
[ 56070-85-0 ]

Yield	Reaction Conditions	Operation in experiment
91%	With selenium(IV) oxide In 1,4-dioxane at 160℃; for 4h; Sealed tube; Inert atmosphere;
91%	With selenium(IV) oxide In 1,4-dioxane at 160℃; for 5h; Inert atmosphere; Sealed tube;
91%	With selenium(IV) oxide In 1,4-dioxane at 160℃; for 5h; Inert atmosphere; Sealed tube;	2 Example 2 Preparation of 4-methoxy-6-aldehyde 2H-pyrone (Compound 3) Under a nitrogen atmosphere, 5.6 g of 4-methoxy-6-methyl-2H-pyrone (Compound 2) was dissolved in 22 g of SeO2The inside of the sealed tube containing 150 mL of dioxane was reacted at a temperature of 160 ° C for 5 hours. After completion of the reaction, the mixture was cooled to room temperatureThe solid was washed with dichloromethane and the crude product was chromatographed to give 5.6 g of solid. The solid product was4-methoxy-6-Aldehyde group2H-pyrone(Numbered Compound 3) in a yield of 91%.

65%	With selenium(IV) oxide In 1,4-dioxane at 180℃; for 5h; Inert atmosphere; Sealed tube;
61%	With selenium(IV) oxide In 1,4-dioxane at 150℃; for 0.25h; Microwave irradiation;
	With selenium(IV) oxide In 1,4-dioxane for 24h; Heating;
362 mg	With selenium(IV) oxide In 1,4-dioxane at 160℃; for 3h;	4.4.1. 6-Formyl-4-methoxy-2H-pyran-2-one (8) The mixture of 4-methoxy-6-methyl-2H-pyran-2-one (7; 500 mg, Sigma-Aldrich, Inc.), SeO2 (1.2 g, Kanto Chemical Co., Inc.) and anhydrous dioxane (5 ml) in a sealed tube was heated at 160°C (outside) and stirred vigorously. After 3 h, the precipitate was removed by filtration and washed with dioxane. The latter was removed by evaporation in vacuo to afford a residue, which was poured into brine (100 ml). The resulting product was extracted with EtOAc (100 ml x 3) with the EtOAc solubles combined. After drying over Na2SO4, the extract was evaporated to dryness. The residue was purified by Si gel flash CC. The column (150 x 20 mm) was developed successively with 300 ml of Me2CO-n-hexane (3:7, 4:6 and 1:1 v/v), respectively. Compound 8 (362 mg) was eluted with Me2CO-n-hexane (4:6, v/v): dH 9.48 (1H, s, 7-H), 6.63 (1H, d, J = 2.3 Hz, 5-H), 5.70 (1H, d, J = 2.3 Hz, 3-H), 3.82 (3H, s, 8-H); EI-MS, 70 eV, m/z 154 (M+, 22%), 125 (100), 69 (20), and 59 (15).
	Multi-step reaction with 2 steps 1.1: magnesium / methanol / 1.5 h / 80 °C / Inert atmosphere; Schlenk technique 2.1: 4-methylmorpholine N-oxide; citric acid; potassium osmate(VI) dihydrate / water; <i>tert</i>-butyl alcohol / 2 h / 20 °C 2.2: 1 h / 20 °C

Reference： [1]Fang, Sai; Chen, Lei; Yu, Miao; Cheng, Bao; Lin, Yongsheng; Morris-Natschke, Susan L.; Lee, Kuo-Hsiung; Gu, Qiong; Xu, Jun [Organic and Biomolecular Chemistry, 2015, vol. 13, # 16, p. 4714 - 4726]
[2]Cheng, Bao; Lin, Yongsheng; Kuang, Ming; Fang, Sai; Gu, Qiong; Xu, Jun; Wang, Laiyou [Chemical Biology and Drug Design, 2015, vol. 86, # 5, p. 1121 - 1130]
[3]Current Patent Assignee: SUN YAT-SEN UNIVERSITY (CHINA) - CN104592182, 2017, B Location in patent: Paragraph 0030; 0031
[4]Location in patent: experimental part Soldi, Cristian; Moro, Angelica V.; Pizzolatti, Moacir G.; Correia, Carlos R. D. [European Journal of Organic Chemistry, 2012, # 19, p. 3607 - 3616]
[5]Fang, Zhanxiong; Liao, Pei-Chun; Yang, Yu-Liang; Yang, Feng-Ling; Chen, Yi-Lin; Lam, Yulin; Hua, Kuo-Feng; Wu, Shih-Hsiung [Journal of Medicinal Chemistry, 2010, vol. 53, # 22, p. 7967 - 7978]
[6]Bacardit, R.; Moreno-Manas, M.; Pleixats, R. [Journal of Heterocyclic Chemistry, 1982, vol. 19, p. 157 - 160]
[7]Location in patent: experimental part Suzuki, Masanobu; Sakuno, Emi; Ishihara, Atsushi; Tamura, Jun-Ichi; Nakajima, Hiromitsu [Phytochemistry, 2012, vol. 75, p. 14 - 20]
[8]Rizzo, Antonio; Trauner, Dirk [Organic Letters, 2018, vol. 20, # 7, p. 1841 - 1844]

9
[ 672-89-9 ]
[ 2174-64-3 ]

Yield	Reaction Conditions	Operation in experiment
95%	With sodium methylate In methanol at 185℃; for 0.5h;
87%	Stage #1: 4-methoxy-6-methyl-2H-pyran-2-one With methanol; sodium Stage #2: at 185℃; for 0.5h; Further stages.;
	With methanol; sodium at 185℃;

Reference： [1]Effenberger, Franz; Schoenwaelder, Karl-Heinz [Chemische Berichte, 1984, vol. 117, # 11, p. 3270 - 3279]
[2]Hansen, Chad A.; Frost [Journal of the American Chemical Society, 2002, vol. 124, # 21, p. 5926 - 5927]
[3]Achkar, Jihane; Xian, Mo; Zhao, Huimin; Frost [Journal of the American Chemical Society, 2005, vol. 127, # 15, p. 5332 - 5333]

10
[ 672-89-9 ]
[ 120-57-0 ]
(E)-6-[2-(benzo[d][1,3]dioxol-5-yl)vinyl]-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	Stage #1: 4-methoxy-6-methyl-2H-pyran-2-one With potassium hexamethylsilazane In tetrahydrofuran at -78℃; for 0.166667h; Inert atmosphere; Stage #2: piperonal In tetrahydrofuran at -78 - 0℃; for 0.666667h; Inert atmosphere; stereoselective reaction;	General Procedure for the synthesis of (E)-4-methoxy-6-styryl-2H-pyran-2-one using KHMDS General procedure: To a solution of Pyrone (1.0 mmol, 1.0 equiv.) in THF (10 mL) was added KHMDS (1M in THF, 1.6 mmol, 1.6 equiv.) at -78 °C under nitrogen and stirred for 10 min, and then aldehyde (1.6 mmol, 1.6 equiv.) in THF (5 mL) was added in dropwise and stirred at -78 °C for 10 min and then slowly warmed to 0 °C over 30 min under stirring. The reaction mixture was quenched with 10 % HCl solution, extracted with DCM, washed with brine, dried over Na2SO4, and concentrated to afford crude product was purified by silica gel (100-200 mesh) column chromatography, eluted with 30-40 % EtOAc in pet ether to afford the corresponding styryl pyrones.
52%	With magnesium methanolate In methanol for 7h; Heating;
13%	With magnesium methanolate In methanol for 20h; Reflux; Inert atmosphere;	General Procedure for Preparation of Kavalactone Analogues 1-19. General procedure: Kavalactone analogues were prepared according to the previously reported method [24]. Amixture of 4-methoxy-6-methyl-pyran-2-one (25 mg, 0.178 mmol) and appropriate aldehyde (0.178mmol) in dimethoxymagnesium solution (60% in 2 mL methanol) was heated to reflux under anitrogen atmosphere for 20 h. After the reaction was completed, the mixture was concentrated underreduced pressure. The crude product was purified by flash column-chromatography (0%-40%EtOAc/cHexane) to give the title compound.

Reference： [1]Basu, Manas K.; Mukkanti, K.; Samala, Ramakrishna [Tetrahedron Letters, 2022, vol. 88]
[2]Adam; Saha-Moller; Veit; Welke [Synthesis, 1994, # 11, p. 1133 - 1134]
[3]Chang, Bill C. H.; Dilrukshi Herath, H. M. P.; Garcia-Bustos, José; Gasser, Robin B.; Hofmann, Andreas; Jabbar, Abdul; Ma, Guangxu; Nguyen, Nghi; Sleebs, Brad E.; Taki, Aya C.; Wang, Tao [Molecules, 2020, vol. 25, # 8]

11
[ 675-10-5 ]
[ 80-48-8 ]
[ 672-89-9 ]

Yield	Reaction Conditions	Operation in experiment
82%	Stage #1: 4-hydroxy-6-methyl-2-pyron; methyl p-toluene sulfonate With potassium carbonate In N,N-dimethyl-formamide at 0 - 20℃; for 22h; Stage #2: In water; N,N-dimethyl-formamide at 20℃; for 0.5h;
79%	With potassium carbonate In N,N-dimethyl-formamide at 3 - 20℃; for 12h;

Reference： [1]Bach, Thorsten; Koser, Lilla; Lechner, Vivian Miles [Angewandte Chemie - International Edition, 2021, vol. 60, # 37, p. 20269 - 20273][Angew. Chem., 2021, vol. 133, # 37, p. 20431 - 20435]
[2]Oikawa, Hideaki; Kobayashi, Tomonori; Katayama, Kinya; Suzuki, Yuichi; Ichihara, Akitami [Journal of Organic Chemistry, 1998, vol. 63, # 24, p. 8748 - 8756]

12
[ 672-89-9 ]
3-Chloro-4-methoxy-6-methyl-2-pyranone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With N-chloro-succinimide In tetrachloromethane for 1h; Heating;
57%	With trichloroisocyanuric acid In ethyl acetate at 85℃; Green chemistry; regioselective reaction;

Reference： [1]Lokot; Pashkovskii; Lakhvich [Russian Journal of Organic Chemistry, 1998, vol. 34, # 9, p. 1350 - 1354]
[2]Prendergast, Aisling M.; McGlacken, Gerard P. [European Journal of Organic Chemistry, 2017, vol. 2017, # 32, p. 4827 - 4835]

13
[ 672-89-9 ]
(+)-5,6-dihydro-4-methoxy-2H-pyran-2-one [ No CAS ]
(-)-5,6-dihydro-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrafluoroboric acid; hydrogen In isopropyl alcohol at 60℃; for 20h; Title compound not separated from byproducts;

Reference： [1]Fehr, Matthias J.; Consiglio, Giambattista; Scalone, Michelangelo; Schmid, Rudolf [Journal of Organic Chemistry, 1999, vol. 64, # 16, p. 5768 - 5776]

14
[ 672-89-9 ]
[ 330151-70-7 ]
[ 221356-83-8 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen; Cinchonin In isopropyl alcohol at 20℃;
	With hydrogen; Cinchonidin In isopropyl alcohol at 20℃; Title compound not separated from byproducts;
	With hydrogen; Cinchonin

	With hydrogen; palladium; Cinchonidin In isopropyl alcohol at 24.85℃; for 1h; Title compound not separated from byproducts;
	With hydrogen; quinidine In isopropyl alcohol at 25℃;
	With 5% Pd/Al2O3; hydrogen; cinchonine In isopropyl alcohol at 20℃; optical yield given as %ee; enantioselective reaction;	Conditions g Before the hydrogenation of 7, the catalyst (20 mg Pd/Al2O3) was prereduced in 5 mL 2-propanol for 5 min with H2 at 2 bar and 20 °C. Then, 3.4 μmol modifier in 5 mL 2-propanol was added and the hydrogenation continued for another 5 min before the reaction was started by the addition of 0.18 mmol substrate in 5 mL 2-propanol.

Reference： [1]Kuenzle, N.; Soler, J.-W.; Mallat, T.; Baiker, A. [Journal of Catalysis, 2002, vol. 210, # 2, p. 466 - 470]
[2]BuÌ¿rgi, Thomas; Baiker, Alfons [Journal of Physical Chemistry B, 2002, vol. 106, # 41, p. 10649 - 10658]
[3]Strobel, Reto; Krumeich, Frank; Stark, Wendelin J.; Pratsinis, Sotiris E.; Baiker, Alfons [Journal of Catalysis, 2004, vol. 222, # 2, p. 307 - 314]
[4]Huck; Buergi; Mallat; Baiker [Journal of Catalysis, 2003, vol. 219, # 1, p. 41 - 51]
[5]Huck, Wolf-Rüdiger; Mallat, Tamas; Baiker, Alfons [Advanced Synthesis and Catalysis, 2003, vol. 345, # 1-2, p. 255 - 260]
[6]Location in patent: experimental part Schmidt, Erik; Bucher, Christoph; Santarossa, Gianluca; Mallat, Tamas; Gilmour, Ryan; Baiker, Alfons [Journal of Catalysis, 2012, vol. 289, p. 238 - 248]

15
[ 672-89-9 ]
[ 120-57-0 ]
6-{2-(benzo[d][1,3]dioxol-5-yl)ethenyl}-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With Pd/C In neat (no solvent) for 0.1h; Microwave irradiation;	Synthesis of 4-methoxy-6-Styryl-2H-pyran-2-ones (general procedure) General procedure: Product III (5 mmol, 0.7 g) and KF-BaO (3 g) were added to the aromatic aldehyde (50 mmol) in minimum amount of methylene chloride. The solvent was evaporated at room temperature under reduced pressure and the process was activated by MWI in a microwave oven at 60 W for 5 min. The product was acidified with HCl, 20% (2 mmol). The residue was dissolved in 10 mL of CH2Cl2 and filtered off. The organic phase was washed with saturated NaCl solution and dried over MgSO4. The solid product was recrystallized from ethanol (0.5 g).
41%	With magnesium methanolate In methanol for 7h; Heating;
40%	With methanol; magnesium for 6h; Inert atmosphere; Reflux;	5.2. General procedure for the preparation of 6-substituted 4-methoxy-2H-pyran-2-ones General procedure: To a suspension of magnesium methoxide, freshly prepared by gently heating Mg (104 mg) in anhydrous MeOH (10 mL), were added 4-methoxy-6-methyl-2-pyrone (11)19 (200 mg, 1.4 mmol) and aldehyde (1.7 mmol) under nitrogen.20 The reaction mixture was heated at reflux for 6 h, allowed to cool and dried in vacuo. The solid was then suspended in acetic acid (3.3 M, 20 mL) and extracted with dichloromethane (4 × 50 mL), and the combined organic layers washed with water (2 × 50 mL) and dried in vacuo. Purification of the resultant pyrone was achieved either by trituration with diethylether followed by recrystallization from MeOH or by silica gel column chromatography eluting with 0-1% MeOH in dichloromethane.

32%

With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 25℃; for 48h;

Representative procedure General procedure: To a stirred solution of 4-methoxy-6-methyl-2-pyrone (0.067 g, 0.47 mmol) in DMF (1 mL) at room temperature was added benzaldehyde (0.1 mL, 0.95 mmol). Potassium tert-butoxide solid (0.1 g,0.95 mmol) was then added portionwise to it and stirred for 2 days at room temperature. Solution became dark red in color. This was extracted withdiethyl ether (3 10 mL). For the compounds 3, 4, 8, 9, 10 methylene chloridewas used for the extraction. The organic layer was washed with brine(3 20 mL), water (5 20 mL), dried over MgSO4, and concentrated in vacuo.The crude product was purified by preparative thin layer chromatography(EtOAc/hexanes) to afford the product.

Reference： [1]Benferrah; Hammadi; Berthiol [Russian Journal of General Chemistry, 2015, vol. 85, # 8, p. 1939 - 1944][Zh. Obshch. Khim., 2015, vol. 85, # 8, p. 1939 - 1944,6]
[2]Park, In-Hye; Jeon, So-Young; Lee, Hee-Ju; Kim, Sang-In; Song, Kyung-Sik [Planta Medica, 2004, vol. 70, # 2, p. 143 - 146]
[3]Location in patent: experimental part McCracken, Stephen T.; Kaiser, Marcel; Boshoff, Helena I.; Boyd, Peter D.W.; Copp, Brent R. [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 4, p. 1482 - 1493]
[4]Kraus, George A.; Wanninayake, Umayangani K. [Tetrahedron Letters, 2015, vol. 56, # 51, p. 7112 - 7114]

16
[ 512-56-1 ]
[ 675-10-5 ]
[ 672-89-9 ]

Yield	Reaction Conditions	Operation in experiment
79%	With potassium carbonate at 140℃; for 1h;

Reference： [1]Hansen, Chad A.; Frost [Journal of the American Chemical Society, 2002, vol. 124, # 21, p. 5926 - 5927]

17
[ 672-89-9 ]
[ 108298-35-7 ]

Yield	Reaction Conditions	Operation in experiment
70%	at 180 - 210℃; for 3h; Neat (no solvent);	5 4-methoxy-6-methyl-pyran-2-one Compound 5a (25.3 g, 180.5 mmol) in DMAD (neat, 33.3 mL, 271.0 mmol) was heated in a round bottom flask at 180 0C for 1 hr and then at 210 °C for 2 hrs. The reaction mixture was cooled to room temperature and concentrated onto SiO2 (75 g), then purified via column chromatography (Horizon, 65% to 60% gradient starting with 5% EtOAc/Hexanes to 20% EtOAc/Hexanes) to afford 5-methoxy-3-methyl-phthalic acid dimethyl ester Compound 5b (30.12 g, 70%) as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 7.29, (d, J = 2.1 Hz, IH), 6.91 (d, 2.0Hz, IH), 3.99 (s, 3H), 3.90 (s, 3H), 3.84 (s, 3H), 234 (s, 3H).

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2007/47646, 2007, A2 Location in patent: Page/Page column 56

18
4-hydroxy-6-methyl-2H-pyran-2-one triacetic acid [ No CAS ]
[ 77-78-1 ]
[ 672-89-9 ]

Yield	Reaction Conditions	Operation in experiment
90%	With potassium carbonate In acetone at 85℃; for 3h; Inert atmosphere;

Reference： [1]Location in patent: experimental part Wadsworth, Andrew D.; Sperry, Jonathan; Brimble, Margaret A. [Synthesis, 2010, # 15, p. 2604 - 2608]

19
[ 98-01-1 ]
[ 672-89-9 ]
6-[2-(furan-2-yl)ethenyl]-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With Pd/C In neat (no solvent) for 0.2h; Microwave irradiation;	Synthesis of 4-methoxy-6-Styryl-2H-pyran-2-ones (general procedure) General procedure: Product III (5 mmol, 0.7 g) and KF-BaO (3 g) were added to the aromatic aldehyde (50 mmol) in minimum amount of methylene chloride. The solvent was evaporated at room temperature under reduced pressure and the process was activated by MWI in a microwave oven at 60 W for 5 min. The product was acidified with HCl, 20% (2 mmol). The residue was dissolved in 10 mL of CH2Cl2 and filtered off. The organic phase was washed with saturated NaCl solution and dried over MgSO4. The solid product was recrystallized from ethanol (0.5 g).
89%	With CaO-KF In dichloromethane at 25℃; for 0.2h; Microwave irradiation;	6-(2-Arylvinyl)-4-methoxy-2H-pyran-2-ones 4a-4d(general procedure). General procedure: The corresponding aromaticaldehyde (20 mmol) was dissolved in a minimumamount of methylene chloride, compound 3 (2.81 g,20 mmol) and KF-CaO (4 g) were added, the solventwas evaporated at room temperature under reducedpressure, and the residue was activated by MWI in amicrowave oven for 5-10 min. The mixture wasacidified with 20% aqueous HCl (4 mmol), dissolvedin 10 mL of of methylene chloride, and filtered, thefiltrate was washed with brine, dried over MgSO4, andevaporated, and the residue was recrystallized from methanol.
21%	With methanol; magnesium for 6h; Inert atmosphere; Reflux;	5.2. General procedure for the preparation of 6-substituted 4-methoxy-2H-pyran-2-ones General procedure: To a suspension of magnesium methoxide, freshly prepared by gently heating Mg (104 mg) in anhydrous MeOH (10 mL), were added 4-methoxy-6-methyl-2-pyrone (11)19 (200 mg, 1.4 mmol) and aldehyde (1.7 mmol) under nitrogen.20 The reaction mixture was heated at reflux for 6 h, allowed to cool and dried in vacuo. The solid was then suspended in acetic acid (3.3 M, 20 mL) and extracted with dichloromethane (4 × 50 mL), and the combined organic layers washed with water (2 × 50 mL) and dried in vacuo. Purification of the resultant pyrone was achieved either by trituration with diethylether followed by recrystallization from MeOH or by silica gel column chromatography eluting with 0-1% MeOH in dichloromethane.

Reference： [1]Benferrah; Hammadi; Berthiol [Russian Journal of General Chemistry, 2015, vol. 85, # 8, p. 1939 - 1944][Zh. Obshch. Khim., 2015, vol. 85, # 8, p. 1939 - 1944,6]
[2]Benferrah; Hammadi; Berthiol [Russian Journal of General Chemistry, 2016, vol. 86, # 12, p. 2881 - 2886][Zh. Obshch. Khim., 2016]
[3]Location in patent: experimental part McCracken, Stephen T.; Kaiser, Marcel; Boshoff, Helena I.; Boyd, Peter D.W.; Copp, Brent R. [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 4, p. 1482 - 1493]

20
[ 672-89-9 ]
[ 66-77-3 ]
4-methoxy-6-[2-(1-naphthyl)ethenyl]-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	With methanol; magnesium for 6h; Inert atmosphere; Reflux;	5.2. General procedure for the preparation of 6-substituted 4-methoxy-2H-pyran-2-ones General procedure: To a suspension of magnesium methoxide, freshly prepared by gently heating Mg (104 mg) in anhydrous MeOH (10 mL), were added 4-methoxy-6-methyl-2-pyrone (11)19 (200 mg, 1.4 mmol) and aldehyde (1.7 mmol) under nitrogen.20 The reaction mixture was heated at reflux for 6 h, allowed to cool and dried in vacuo. The solid was then suspended in acetic acid (3.3 M, 20 mL) and extracted with dichloromethane (4 × 50 mL), and the combined organic layers washed with water (2 × 50 mL) and dried in vacuo. Purification of the resultant pyrone was achieved either by trituration with diethylether followed by recrystallization from MeOH or by silica gel column chromatography eluting with 0-1% MeOH in dichloromethane.

Reference： [1]Location in patent: experimental part McCracken, Stephen T.; Kaiser, Marcel; Boshoff, Helena I.; Boyd, Peter D.W.; Copp, Brent R. [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 4, p. 1482 - 1493]

21
[ 672-89-9 ]
[ 555-16-8 ]
4-methoxy-6-(p-nitrostyryl)-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With Pd/C In neat (no solvent) for 0.133333h; Microwave irradiation;	Synthesis of 4-methoxy-6-Styryl-2H-pyran-2-ones (general procedure) General procedure: Product III (5 mmol, 0.7 g) and KF-BaO (3 g) were added to the aromatic aldehyde (50 mmol) in minimum amount of methylene chloride. The solvent was evaporated at room temperature under reduced pressure and the process was activated by MWI in a microwave oven at 60 W for 5 min. The product was acidified with HCl, 20% (2 mmol). The residue was dissolved in 10 mL of CH2Cl2 and filtered off. The organic phase was washed with saturated NaCl solution and dried over MgSO4. The solid product was recrystallized from ethanol (0.5 g).
5%	With methanol; magnesium for 6h; Inert atmosphere; Reflux;	5.2. General procedure for the preparation of 6-substituted 4-methoxy-2H-pyran-2-ones General procedure: To a suspension of magnesium methoxide, freshly prepared by gently heating Mg (104 mg) in anhydrous MeOH (10 mL), were added 4-methoxy-6-methyl-2-pyrone (11)19 (200 mg, 1.4 mmol) and aldehyde (1.7 mmol) under nitrogen.20 The reaction mixture was heated at reflux for 6 h, allowed to cool and dried in vacuo. The solid was then suspended in acetic acid (3.3 M, 20 mL) and extracted with dichloromethane (4 × 50 mL), and the combined organic layers washed with water (2 × 50 mL) and dried in vacuo. Purification of the resultant pyrone was achieved either by trituration with diethylether followed by recrystallization from MeOH or by silica gel column chromatography eluting with 0-1% MeOH in dichloromethane.

Reference： [1]Benferrah; Hammadi; Berthiol [Russian Journal of General Chemistry, 2015, vol. 85, # 8, p. 1939 - 1944][Zh. Obshch. Khim., 2015, vol. 85, # 8, p. 1939 - 1944,6]
[2]Location in patent: experimental part McCracken, Stephen T.; Kaiser, Marcel; Boshoff, Helena I.; Boyd, Peter D.W.; Copp, Brent R. [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 4, p. 1482 - 1493]

22
[ 672-89-9 ]
[ 100-52-7 ]
[ 1952-41-6 ]

Yield	Reaction Conditions	Operation in experiment
88%	With Pd/C In neat (no solvent) for 0.15h; Microwave irradiation;	Synthesis of 4-methoxy-6-Styryl-2H-pyran-2-ones (general procedure) General procedure: Product III (5 mmol, 0.7 g) and KF-BaO (3 g) were added to the aromatic aldehyde (50 mmol) in minimum amount of methylene chloride. The solvent was evaporated at room temperature under reduced pressure and the process was activated by MWI in a microwave oven at 60 W for 5 min. The product was acidified with HCl, 20% (2 mmol). The residue was dissolved in 10 mL of CH2Cl2 and filtered off. The organic phase was washed with saturated NaCl solution and dried over MgSO4. The solid product was recrystallized from ethanol (0.5 g).
88%	With CaO-KF In dichloromethane at 25℃; for 0.15h; Microwave irradiation;	6-(2-Arylvinyl)-4-methoxy-2H-pyran-2-ones 4a-4d(general procedure). General procedure: The corresponding aromaticaldehyde (20 mmol) was dissolved in a minimumamount of methylene chloride, compound 3 (2.81 g,20 mmol) and KF-CaO (4 g) were added, the solventwas evaporated at room temperature under reducedpressure, and the residue was activated by MWI in amicrowave oven for 5-10 min. The mixture wasacidified with 20% aqueous HCl (4 mmol), dissolvedin 10 mL of of methylene chloride, and filtered, thefiltrate was washed with brine, dried over MgSO4, andevaporated, and the residue was recrystallized from methanol.
56%	With magnesium methanolate Reflux; Inert atmosphere;	Synthesis of β-Lactones Milkbase Compounds (Compounds 3-14): Compound 2 (5 mmol), the corresponding aldehyde (5 mmol), magnesium methoxide (5 mL), refluxing, and nitrogen overnight, TLC detection reaction. After the reaction was completed, the solvent was removed under reduced pressure with mobile phase cyclohexane: ethyl acetate (v /ν) 1:2 over a silica gel column to give compound 3-14; yield: 32-59%

47%	With methanol; magnesium for 6h; Inert atmosphere; Reflux;	5.2. General procedure for the preparation of 6-substituted 4-methoxy-2H-pyran-2-ones General procedure: To a suspension of magnesium methoxide, freshly prepared by gently heating Mg (104 mg) in anhydrous MeOH (10 mL), were added 4-methoxy-6-methyl-2-pyrone (11)19 (200 mg, 1.4 mmol) and aldehyde (1.7 mmol) under nitrogen.20 The reaction mixture was heated at reflux for 6 h, allowed to cool and dried in vacuo. The solid was then suspended in acetic acid (3.3 M, 20 mL) and extracted with dichloromethane (4 × 50 mL), and the combined organic layers washed with water (2 × 50 mL) and dried in vacuo. Purification of the resultant pyrone was achieved either by trituration with diethylether followed by recrystallization from MeOH or by silica gel column chromatography eluting with 0-1% MeOH in dichloromethane.
9.8 g	With magnesium In methanol at 80℃; for 1.5h; Inert atmosphere; Schlenk technique;
122 mg	With magnesium In methanol at 80℃; for 3h;	S1.17. Synthesis of 1f To a dry-MeOH (10 mL), Mg (500 mg, 20.6 mmol) was added and stirred for 30 min. Then benzaldehyde (1mL, 9.8 mmol) and 1e (377.3 mg, 2.7 mmol) dissolved in dry-MeOH was added then stirred 3 hr at 80 °C with reflux condenser. After concentration under reduced pressure, resultant mixture was dissolved in EtOAc and washed with AcOH/H2O (1/4). The EtOAc phase was purified on silica gel open column chromatography (hexane:EtOAc = 3:1) and obtained (1f, 122.0 mg, 0.53 mmol). The NMR data were identical with that of previous report.

Reference： [1]Benferrah; Hammadi; Berthiol [Russian Journal of General Chemistry, 2015, vol. 85, # 8, p. 1939 - 1944][Zh. Obshch. Khim., 2015, vol. 85, # 8, p. 1939 - 1944,6]
[2]Benferrah; Hammadi; Berthiol [Russian Journal of General Chemistry, 2016, vol. 86, # 12, p. 2881 - 2886][Zh. Obshch. Khim., 2016]
[3]Current Patent Assignee: SUN YAT-SEN UNIVERSITY (CHINA) - CN107793353, 2018, A Location in patent: Paragraph 0040; 0043; 0045
[4]Location in patent: experimental part McCracken, Stephen T.; Kaiser, Marcel; Boshoff, Helena I.; Boyd, Peter D.W.; Copp, Brent R. [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 4, p. 1482 - 1493]
[5]Rizzo, Antonio; Trauner, Dirk [Organic Letters, 2018, vol. 20, # 7, p. 1841 - 1844]
[6]Matsumoto, Takahiro; Kitagawa, Takahiro; Imahori, Daisuke; Matsuzaki, Atsushi; Saito, Youhei; Ohta, Tomoe; Yoshida, Tatsusada; Nakayama, Yuji; Ashihara, Eishi; Watanabe, Tetsushi [Bioorganic and Medicinal Chemistry Letters, 2021, vol. 45]

23
[ 672-89-9 ]
[ 120-14-9 ]
6-[2-(3,4-dimethoxyphenyl)ethenyl]-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With Pd/C In neat (no solvent) for 0.166667h; Microwave irradiation;	Synthesis of 4-methoxy-6-Styryl-2H-pyran-2-ones (general procedure) General procedure: Product III (5 mmol, 0.7 g) and KF-BaO (3 g) were added to the aromatic aldehyde (50 mmol) in minimum amount of methylene chloride. The solvent was evaporated at room temperature under reduced pressure and the process was activated by MWI in a microwave oven at 60 W for 5 min. The product was acidified with HCl, 20% (2 mmol). The residue was dissolved in 10 mL of CH2Cl2 and filtered off. The organic phase was washed with saturated NaCl solution and dried over MgSO4. The solid product was recrystallized from ethanol (0.5 g).
79%	With CaO-KF In dichloromethane at 25℃; for 0.166667h; Microwave irradiation;	6-(2-Arylvinyl)-4-methoxy-2H-pyran-2-ones 4a-4d(general procedure). General procedure: The corresponding aromaticaldehyde (20 mmol) was dissolved in a minimumamount of methylene chloride, compound 3 (2.81 g,20 mmol) and KF-CaO (4 g) were added, the solventwas evaporated at room temperature under reducedpressure, and the residue was activated by MWI in amicrowave oven for 5-10 min. The mixture wasacidified with 20% aqueous HCl (4 mmol), dissolvedin 10 mL of of methylene chloride, and filtered, thefiltrate was washed with brine, dried over MgSO4, andevaporated, and the residue was recrystallized frommethanol.
28%	With methanol; magnesium for 6h; Inert atmosphere; Reflux;	5.2. General procedure for the preparation of 6-substituted 4-methoxy-2H-pyran-2-ones General procedure: To a suspension of magnesium methoxide, freshly prepared by gently heating Mg (104 mg) in anhydrous MeOH (10 mL), were added 4-methoxy-6-methyl-2-pyrone (11)19 (200 mg, 1.4 mmol) and aldehyde (1.7 mmol) under nitrogen.20 The reaction mixture was heated at reflux for 6 h, allowed to cool and dried in vacuo. The solid was then suspended in acetic acid (3.3 M, 20 mL) and extracted with dichloromethane (4 × 50 mL), and the combined organic layers washed with water (2 × 50 mL) and dried in vacuo. Purification of the resultant pyrone was achieved either by trituration with diethylether followed by recrystallization from MeOH or by silica gel column chromatography eluting with 0-1% MeOH in dichloromethane.

Reference： [1]Benferrah; Hammadi; Berthiol [Russian Journal of General Chemistry, 2015, vol. 85, # 8, p. 1939 - 1944][Zh. Obshch. Khim., 2015, vol. 85, # 8, p. 1939 - 1944,6]
[2]Benferrah; Hammadi; Berthiol [Russian Journal of General Chemistry, 2016, vol. 86, # 12, p. 2881 - 2886][Zh. Obshch. Khim., 2016]
[3]Location in patent: experimental part McCracken, Stephen T.; Kaiser, Marcel; Boshoff, Helena I.; Boyd, Peter D.W.; Copp, Brent R. [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 4, p. 1482 - 1493]

24
[ 672-89-9 ]
[ 104-55-2 ]
4-methoxy-6-(4-phenyl-1,3-butadienyl)-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 25℃; for 48h;	Representative procedure General procedure: To a stirred solution of 4-methoxy-6-methyl-2-pyrone (0.067 g, 0.47 mmol) in DMF (1 mL) at room temperature was added benzaldehyde (0.1 mL, 0.95 mmol). Potassium tert-butoxide solid (0.1 g,0.95 mmol) was then added portionwise to it and stirred for 2 days at room temperature. Solution became dark red in color. This was extracted withdiethyl ether (3 10 mL). For the compounds 3, 4, 8, 9, 10 methylene chloridewas used for the extraction. The organic layer was washed with brine(3 20 mL), water (5 20 mL), dried over MgSO4, and concentrated in vacuo.The crude product was purified by preparative thin layer chromatography(EtOAc/hexanes) to afford the product.
6%	With methanol; magnesium for 6h; Inert atmosphere; Reflux;	5.2. General procedure for the preparation of 6-substituted 4-methoxy-2H-pyran-2-ones General procedure: To a suspension of magnesium methoxide, freshly prepared by gently heating Mg (104 mg) in anhydrous MeOH (10 mL), were added 4-methoxy-6-methyl-2-pyrone (11)19 (200 mg, 1.4 mmol) and aldehyde (1.7 mmol) under nitrogen.20 The reaction mixture was heated at reflux for 6 h, allowed to cool and dried in vacuo. The solid was then suspended in acetic acid (3.3 M, 20 mL) and extracted with dichloromethane (4 × 50 mL), and the combined organic layers washed with water (2 × 50 mL) and dried in vacuo. Purification of the resultant pyrone was achieved either by trituration with diethylether followed by recrystallization from MeOH or by silica gel column chromatography eluting with 0-1% MeOH in dichloromethane.

Reference： [1]Kraus, George A.; Wanninayake, Umayangani K. [Tetrahedron Letters, 2015, vol. 56, # 51, p. 7112 - 7114]
[2]Location in patent: experimental part McCracken, Stephen T.; Kaiser, Marcel; Boshoff, Helena I.; Boyd, Peter D.W.; Copp, Brent R. [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 4, p. 1482 - 1493]

25
[ 672-89-9 ]
4-Methoxy-6-methyl-5,6-dihydro-2-pyranone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 5% Pd/Al2O3; hydrogen In isopropyl alcohol at 20℃;	Conditions g Before the hydrogenation of 7, the catalyst (20 mg Pd/Al2O3) was prereduced in 5 mL 2-propanol for 5 min with H2 at 2 bar and 20 °C. Then, 3.4 μmol modifier in 5 mL 2-propanol was added and the hydrogenation continued for another 5 min before the reaction was started by the addition of 0.18 mmol substrate in 5 mL 2-propanol.

Reference： [1]Location in patent: experimental part Schmidt, Erik; Bucher, Christoph; Santarossa, Gianluca; Mallat, Tamas; Gilmour, Ryan; Baiker, Alfons [Journal of Catalysis, 2012, vol. 289, p. 238 - 248]

26
[ 672-89-9 ]
6-(tert-butyldiphenylsilyloxy)-2-phenyl-3a,7a-bis(trimethylsilyloxy)-5,6,7,7a-tetrahydrobenzofuran-4(3aH)-one [ No CAS ]
6-[(6-(tert-butyldiphenylsilyloxy)-4-hydroxy-2-phenyl-3a,7a-bis(trimethylsilyloxy)-3a,4,5,6,7,7a-hexahydrobenzofuran-4-yl)methyl]-4-methoxy-2H-pyran-2-one [ No CAS ]
6-[(6-(tert-butyldiphenylsilyloxy)-4-hydroxy-2-phenyl-3a,7a-bis(trimethylsilyloxy)-3a,4,5,6,7,7a-hexahydrobenzofuran-4-yl)methyl]-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-methoxy-6-methyl-2H-pyran-2-one With n-butyllithium; diisopropylamine In tetrahydrofuran at -78℃; for 0.416667h; Inert atmosphere; Stage #2: 6-(tert-butyldiphenylsilyloxy)-2-phenyl-3a,7a-bis(trimethylsilyloxy)-5,6,7,7a-tetrahydrobenzofuran-4(3aH)-one In tetrahydrofuran at -78℃; for 0.333333h; Inert atmosphere; Overall yield = 51 %; Overall yield = 254 mg; Optical yield = 71.014 %de; diastereoselective reaction;	6-[(6-(tert-Butyldiphenylsilyloxy)-4-hydroxy-2-phenyl-3a,7abis(trimethylsilyloxy)-3a,4,5,6,7,7a-hexahydrobenzofuran-4-yl)methyl)-4-methoxy-2H-pyran-2-one (24) LDA was prepared freshly by slowly adding n-BuLi (1.6 M in THF) (1.61 mL, 2.57 mmol) to a solution of i-Pr2NH (0.41 mL, 2.92 mmol) in anhydrous THF (8.5 mL) at -78 °C. The solution was stirred 15 min at -78 °C and then 5 min at r.t., and then cooled to -78 °C. Methylpyrone 618 (369 mg, 2.63 mmol) in anhydrous THF (10 mL) was slowly added to the LDA solution at -78 °C. The reaction mixture was stirred 25 min at -78 °C. A solution of enol silyl acetal 23 (404 mg, 0.63 mmol) in anhydrous THF (8.5 mL) was slowly added to the mixture at -78 °C and stirred for 20 min at this temperature. Sat. aq NH4Cl (20 mL) was added to the mixture with subsequent stirring for 5 min at r.t. The aqueous layer was extracted with CH2Cl2 (5 × 15 mL) and the combined organic layers were washed with brine (25 mL) and dried (Na2SO4). The solvent was removed under reduced pressure and the crude product purified by flash chromatography on silica gel (pentane-EtOAc, 3:1 to 2:1) to give 24 (254 mg, 322 μmol, 51%) with a dr of 5.9:1 as a white foam; Rf = 0.69 (pentane-EtOAc, 1:1). IR (ATR, neat): 3066 (w), 2957 (w), 2897 (w), 2859 (w), 1724 (m), 1646 (w), 1569 (w), 1454 (w), 1420 (w), 1314 (w), 1250 (m), 1196 (w), 1135 (w), 1102 (m), 997 (w), 919 (m), 897 (m), 842 (s), 740 (m), 699 (s), 613 (w), 545 (w), 505 (w), 405 cm-1 (w). 1H NMR (300 MHz, CD2Cl2): δ (cis-isomer) = 7.59-7.55 (m, 2 H,), 7.55-7.52 (m, 2 H,), 7.38-7.23 (m, 11 H,), 5.94 (d, J = 2.3 Hz, 1 H), 5.42 (d, J = 2.3 Hz, 1 H), 5.07 (s, 1 H), 3.97-3.90 (m, 1 H), 3.82 (s, 3 H), 3.04 (d, J = 1.9 Hz, 1 H), 2.86 (d, J = 14.0 Hz, 1 H), 2.65 (t, J = 11.9 Hz, 1 H), 2.45 (d, J = 13.9 Hz, 1 H), 2.24 (dd, J = 12.2, 4.9 Hz, 1 H), 1.92 (ddd, J = 15.0, 8.4, 2.0 Hz, 1 H), 1.83 (dd, J = 15.0,5.7 Hz, 1 H), 0.99 (s, 9 H), 0.17 (s, 9 H,), 0.11 (s, 9 H); δ (trans-isomer)= 7.68-7.59 (m, 4 H), 7.48-7.28 (m, 11 H), 5.80 (d, J = 2.2 Hz, 1 H), 5.40 (d, J = 2.2 Hz, 1 H), 5.35 (s, 1 H), 4.21-4.08 (m, 1H), 3.80 (s, 3 H), 2.76 (d, J = 14.5 Hz, 1 H), 2.64 (d, J = 14.5 Hz, 1H), 2.49 (dd, J = 13.8, 5.1 Hz, 1 H), 2.02-1.95 (m, 1 H), 1.95-1.76 (m, 2 H), 1.06 (s, 9 H), 0.16 (s, 9 H), 0.08 (s, 9 H). 13C NMR (125 MHz, CD2Cl2): δ (cis-isomer) = 171.4, 164.9, 162.9, 158.5, 136.1 (2 C), 136.0 (2 C), 134.5, 134.3, 130.0 (2 C), 130.0, 129.9, 128.7 (2 C), 128.0 (2 C), 127.9 (2 C), 126.1 (2 C), 109.4, 103.1, 97.0, 88.1, 87.8, 78.2, 65.1, 56.3, 43.8, 43.1, 40.2, 27.1 (3 C), 19.3, 2.2 (3 C), 2.1 (3 C); δ (trans-isomer) = 171.3, 164.7, 163.2, 157.2, 136.2 (2 C), 136.1 (2 C), 134.8, 134.6, 130.3, 130.0, 130.0, 129.8, 128.7 (2 C), 128.0 (2 C), 127.9 (2 C), 125.9 (2 C), 109.6, 103.2, 99.0, 89.2, 88.0, 76.9, 65.4, 56.3, 43.9, 43.0, 39.7, 27.2 (3 C), 19.4, 2.4 (3 C), 2.1 (3 C). HRMS (EI): m/z calcd for C43H56O8Si3 [M]+: 784.3283; found: 784.3270.

Reference： [1]Seitz, Tobias; Harms, Klaus; Koert, Ulrich [Synthesis, 2014, vol. 46, # 3, p. 381 - 386]

27
[ 672-89-9 ]
[ 104-88-1 ]
4-methoxy-6-(p-chlorostyryl)-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With Pd/C In neat (no solvent) for 0.116667h; Microwave irradiation;	Synthesis of 4-methoxy-6-Styryl-2H-pyran-2-ones (general procedure) General procedure: Product III (5 mmol, 0.7 g) and KF-BaO (3 g) were added to the aromatic aldehyde (50 mmol) in minimum amount of methylene chloride. The solvent was evaporated at room temperature under reduced pressure and the process was activated by MWI in a microwave oven at 60 W for 5 min. The product was acidified with HCl, 20% (2 mmol). The residue was dissolved in 10 mL of CH2Cl2 and filtered off. The organic phase was washed with saturated NaCl solution and dried over MgSO4. The solid product was recrystallized from ethanol (0.5 g).

Reference： [1]Benferrah; Hammadi; Berthiol [Russian Journal of General Chemistry, 2015, vol. 85, # 8, p. 1939 - 1944][Zh. Obshch. Khim., 2015, vol. 85, # 8, p. 1939 - 1944,6]

28
[ 672-89-9 ]
[ 123-11-5 ]
6-(4-methoxystyryl)-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With Pd/C In neat (no solvent) for 0.166667h; Microwave irradiation;	Synthesis of 4-methoxy-6-Styryl-2H-pyran-2-ones (general procedure) General procedure: Product III (5 mmol, 0.7 g) and KF-BaO (3 g) were added to the aromatic aldehyde (50 mmol) in minimum amount of methylene chloride. The solvent was evaporated at room temperature under reduced pressure and the process was activated by MWI in a microwave oven at 60 W for 5 min. The product was acidified with HCl, 20% (2 mmol). The residue was dissolved in 10 mL of CH2Cl2 and filtered off. The organic phase was washed with saturated NaCl solution and dried over MgSO4. The solid product was recrystallized from ethanol (0.5 g).

Reference： [1]Benferrah; Hammadi; Berthiol [Russian Journal of General Chemistry, 2015, vol. 85, # 8, p. 1939 - 1944][Zh. Obshch. Khim., 2015, vol. 85, # 8, p. 1939 - 1944,6]

29
[ 672-89-9 ]
[ 86-81-7 ]
[ 60427-79-4 ]

Yield	Reaction Conditions	Operation in experiment
90%	With Pd/C In neat (no solvent) for 0.166667h; Microwave irradiation;	Synthesis of 4-methoxy-6-Styryl-2H-pyran-2-ones (general procedure) General procedure: Product III (5 mmol, 0.7 g) and KF-BaO (3 g) were added to the aromatic aldehyde (50 mmol) in minimum amount of methylene chloride. The solvent was evaporated at room temperature under reduced pressure and the process was activated by MWI in a microwave oven at 60 W for 5 min. The product was acidified with HCl, 20% (2 mmol). The residue was dissolved in 10 mL of CH2Cl2 and filtered off. The organic phase was washed with saturated NaCl solution and dried over MgSO4. The solid product was recrystallized from ethanol (0.5 g).
90%	With CaO-KF In dichloromethane at 25℃; for 0.166667h; Microwave irradiation;	6-(2-Arylvinyl)-4-methoxy-2H-pyran-2-ones 4a-4d(general procedure). General procedure: The corresponding aromaticaldehyde (20 mmol) was dissolved in a minimumamount of methylene chloride, compound 3 (2.81 g,20 mmol) and KF-CaO (4 g) were added, the solventwas evaporated at room temperature under reducedpressure, and the residue was activated by MWI in amicrowave oven for 5-10 min. The mixture wasacidified with 20% aqueous HCl (4 mmol), dissolvedin 10 mL of of methylene chloride, and filtered, thefiltrate was washed with brine, dried over MgSO4, andevaporated, and the residue was recrystallized frommethanol. 4-Methoxy-6-[2-(3,4,5-trimethoxyphenyl)ethenyl)]-2H-pyran-2-one (4a) was synthesized from 3,4,5-trimethoxybenzaldehyde(3.92 g, 20 mmol), MW power40W, irradiation time 10 min. Yield 90%, yellowsolid, mp 201°C. IR spectrum, ν, cm-1: 1707 (C=O),1645, 1585, 1553, 1511, 1455, 1409, 1342, 1255, 1152, 1009, 842, 817. 1 NMR spectrum, δ, ppm: 3.85s (3H, OCH3), 3.90 s (3H, OCH3), 3.92 s (3H, OCH3),3.94 s (3H,OCH3), 5.52 d (1H, 3-H), 5.98 d (1H, 5-H),6.52 d (1H, α-H), 6.79 s (2H, 2′-H, 6′-H), 7.45 d (1H,β-H). 13 NMR spectrum δC, ppm: 55.8 (4′-OCH3),56.1 (3′-OCH3, 5′-OCH3), 60.8 (4-OCH3), 88.7 (C3),100.2 (C5), 104.6 (C2′, C6′), 117.8 (Cα), 119.6(C4′),130.7 (C1′), 135.7 (Cβ),153.4 (C3′, C5′), 158.5 (C6),163.9 (C2), 171.07 (C4). Mass spectrum, m/z (Irel, %):318 (64) [M]+, 275 (9.4), 181 (4), 149 (27), 69 (100),65 (47). C17H18O6. Calculated: M 318.33.

Reference： [1]Benferrah; Hammadi; Berthiol [Russian Journal of General Chemistry, 2015, vol. 85, # 8, p. 1939 - 1944][Zh. Obshch. Khim., 2015, vol. 85, # 8, p. 1939 - 1944,6]
[2]Benferrah; Hammadi; Berthiol [Russian Journal of General Chemistry, 2016, vol. 86, # 12, p. 2881 - 2886][Zh. Obshch. Khim., 2016]

30
[ 672-89-9 ]
[ 1122-91-4 ]
6-(4-bromostyryl)-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With Pd/C In neat (no solvent) for 0.133333h; Microwave irradiation;	Synthesis of 4-methoxy-6-Styryl-2H-pyran-2-ones (general procedure) General procedure: Product III (5 mmol, 0.7 g) and KF-BaO (3 g) were added to the aromatic aldehyde (50 mmol) in minimum amount of methylene chloride. The solvent was evaporated at room temperature under reduced pressure and the process was activated by MWI in a microwave oven at 60 W for 5 min. The product was acidified with HCl, 20% (2 mmol). The residue was dissolved in 10 mL of CH2Cl2 and filtered off. The organic phase was washed with saturated NaCl solution and dried over MgSO4. The solid product was recrystallized from ethanol (0.5 g).

Reference： [1]Benferrah; Hammadi; Berthiol [Russian Journal of General Chemistry, 2015, vol. 85, # 8, p. 1939 - 1944][Zh. Obshch. Khim., 2015, vol. 85, # 8, p. 1939 - 1944,6]

31
[ 672-89-9 ]
[ 459-57-4 ]
6-(4-fluorostyryl)-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With Pd/C In neat (no solvent) for 0.166667h; Microwave irradiation;	Synthesis of 4-methoxy-6-Styryl-2H-pyran-2-ones (general procedure) General procedure: Product III (5 mmol, 0.7 g) and KF-BaO (3 g) were added to the aromatic aldehyde (50 mmol) in minimum amount of methylene chloride. The solvent was evaporated at room temperature under reduced pressure and the process was activated by MWI in a microwave oven at 60 W for 5 min. The product was acidified with HCl, 20% (2 mmol). The residue was dissolved in 10 mL of CH2Cl2 and filtered off. The organic phase was washed with saturated NaCl solution and dried over MgSO4. The solid product was recrystallized from ethanol (0.5 g).

Reference： [1]Benferrah; Hammadi; Berthiol [Russian Journal of General Chemistry, 2015, vol. 85, # 8, p. 1939 - 1944][Zh. Obshch. Khim., 2015, vol. 85, # 8, p. 1939 - 1944,6]

32
[ 98-03-3 ]
[ 672-89-9 ]
[ 60427-80-7 ]

Yield	Reaction Conditions	Operation in experiment
82%	With Pd/C In neat (no solvent) for 0.15h; Microwave irradiation;	Synthesis of 4-methoxy-6-Styryl-2H-pyran-2-ones (general procedure) General procedure: Product III (5 mmol, 0.7 g) and KF-BaO (3 g) were added to the aromatic aldehyde (50 mmol) in minimum amount of methylene chloride. The solvent was evaporated at room temperature under reduced pressure and the process was activated by MWI in a microwave oven at 60 W for 5 min. The product was acidified with HCl, 20% (2 mmol). The residue was dissolved in 10 mL of CH2Cl2 and filtered off. The organic phase was washed with saturated NaCl solution and dried over MgSO4. The solid product was recrystallized from ethanol (0.5 g).

Reference： [1]Benferrah; Hammadi; Berthiol [Russian Journal of General Chemistry, 2015, vol. 85, # 8, p. 1939 - 1944][Zh. Obshch. Khim., 2015, vol. 85, # 8, p. 1939 - 1944,6]

33
[ 672-89-9 ]
[ 123-11-5 ]
[ 500-62-9 ]

Yield	Reaction Conditions	Operation in experiment
61%	With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 25℃; for 48h;	Representative procedure General procedure: To a stirred solution of 4-methoxy-6-methyl-2-pyrone (0.067 g, 0.47 mmol) in DMF (1 mL) at room temperature was added benzaldehyde (0.1 mL, 0.95 mmol). Potassium tert-butoxide solid (0.1 g,0.95 mmol) was then added portionwise to it and stirred for 2 days at room temperature. Solution became dark red in color. This was extracted withdiethyl ether (3 10 mL). For the compounds 3, 4, 8, 9, 10 methylene chloridewas used for the extraction. The organic layer was washed with brine(3 20 mL), water (5 20 mL), dried over MgSO4, and concentrated in vacuo.The crude product was purified by preparative thin layer chromatography(EtOAc/hexanes) to afford the product.
59%	With magnesium methanolate Inert atmosphere; Reflux;	3.1.2 General procedure for the preparation of compounds 3-14 General procedure: Compound 2 (2.40mmol) and appropriate aldehydes (2.40mmol) in the presence of Mg(OCH3)2 (10mL) was refluxed under N2 overnight. After the reaction was completed as indicated by TLC, the mixture was concentrated under reduced pressure. The residue was purified with silica gel chromatography to obtain target compounds 3-14.
30%	With magnesium In methanol for 4h; Reflux;

23%	With magnesium methanolate In methanol at 60℃;	General procedure for the synthesis of compounds 1, 4-22, 27-29 General procedure: The synthesis of 5,6-dehydrokawain analogues were performed based on the method reported by McCracken, S. T. et al.2 Magnesium methoxide was prepared by gently heating Mg (156 mg) in anhydrous MeOH. 4-Methoxy-6-methyl-2-pyrone (3)3 (0.30 g, 2.1 mmol) or other 2-pyrones and each aldehyde (2.2 mmol) were added to the solution. The reaction mixture was heated at reflux for 3-6 hours, cooled, and dried in vacuo. The residual material was then suspended in acetic acid (3.3 M, 30 mL) and extracted with ethyl acetate for three times. The combined organic layer was washed with water and dried in vacuo. Purification of the compounds was conducted by preparative HPLC. NMR spectra were recorded on a JEOL JNM-ECZ400S in CDCl3. HRMS was recorded on a Thermo scientific Q Exactive instrument. Mp were recorded on a Yanagimoto micro melting point apparatus. The 1H and 13C NMR data observed for 11,4, 33, 73, 83, 105, 222, 256, 266 were agreed with those previously reported in the literature. The 1H NMR data of 247 and 278 were in agreement with literature values.
23%	With magnesium In methanol at 60℃; for 5h;	1 Compound 20: 4-Methoxy-6 - [(E) -2- (4-methoxyphenyl) vinyl] -2H-pyran-2-one (formula (20)) Metal Mg was heated in methanol (60 ° C.) and suspended. 4-methoxy-6-methyl-2-pyrone (0.20 g) and 4-methoxybenzaldehyde (0.20 ml, 1.6 mmol) were added thereto, and the mixture was heated at 60 ° C. for 5 hours. After cooling, it was acidified with acetic acid and extracted with ethyl acetate. The extract was concentrated under reduced pressure and then purified by reverse phase preparative HPLC (mobile phase: water-acetonitrile = 3: 7).Yield: 23%.
22%	With magnesium methanolate In methanol for 20h; Reflux; Inert atmosphere;	General Procedure for Preparation of Kavalactone Analogues 1-19. General procedure: Kavalactone analogues were prepared according to the previously reported method [24]. Amixture of 4-methoxy-6-methyl-pyran-2-one (25 mg, 0.178 mmol) and appropriate aldehyde (0.178mmol) in dimethoxymagnesium solution (60% in 2 mL methanol) was heated to reflux under anitrogen atmosphere for 20 h. After the reaction was completed, the mixture was concentrated underreduced pressure. The crude product was purified by flash column-chromatography (0%-40%EtOAc/cHexane) to give the title compound.

Reference： [1]Kraus, George A.; Wanninayake, Umayangani K. [Tetrahedron Letters, 2015, vol. 56, # 51, p. 7112 - 7114]
[2]Li, Chanjuan; Cheng, Bao; Fang, Sai; Zhou, Huihao; Gu, Qiong; Xu, Jun [European Journal of Medicinal Chemistry, 2018, vol. 143, p. 114 - 122]
[3]Purtov, Konstantin V.; Petushkov, Valentin N.; Baranov, Mikhail S.; Mineev, Konstantin S.; Rodionova, Natalja S.; Kaskova, Zinaida M.; Tsarkova, Aleksandra S.; Petunin, Alexei I.; Bondar, Vladimir S.; Rodicheva, Emma K.; Medvedeva, Svetlana E.; Oba, Yuichi; Oba, Yumiko; Arseniev, Alexander S.; Lukyanov, Sergey; Gitelson, Josef I.; Yampolsky, Ilia V. [Angewandte Chemie - International Edition, 2015, vol. 54, # 28, p. 8124 - 8128][Angew. Chem., 2015, vol. 127, # 28, p. 8242 - 8246]
[4]Kumagai, Momochika; Nishikawa, Keisuke; Mishima, Takashi; Yoshida, Izumi; Ide, Masahiro; Koizumi, Keiko; Nakamura, Munetomo; Morimoto, Yoshiki [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 11, p. 2401 - 2406]
[5]Current Patent Assignee: JAPAN FOOD RES LAB - JP2018/123111, 2018, A Location in patent: Paragraph 0055
[6]Chang, Bill C. H.; Dilrukshi Herath, H. M. P.; Garcia-Bustos, José; Gasser, Robin B.; Hofmann, Andreas; Jabbar, Abdul; Ma, Guangxu; Nguyen, Nghi; Sleebs, Brad E.; Taki, Aya C.; Wang, Tao [Molecules, 2020, vol. 25, # 8]

34
[ 672-89-9 ]
[ 100-52-7 ]
5,6-dehydrokawain [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: 4-methoxy-6-methyl-2H-pyran-2-one With potassium hexamethylsilazane In tetrahydrofuran at -78℃; for 0.166667h; Inert atmosphere; Stage #2: benzaldehyde In tetrahydrofuran at -78 - 0℃; for 0.666667h; Inert atmosphere; stereoselective reaction;	General Procedure for the synthesis of (E)-4-methoxy-6-styryl-2H-pyran-2-one using KHMDS General procedure: To a solution of Pyrone (1.0 mmol, 1.0 equiv.) in THF (10 mL) was added KHMDS (1M in THF, 1.6 mmol, 1.6 equiv.) at -78 °C under nitrogen and stirred for 10 min, and then aldehyde (1.6 mmol, 1.6 equiv.) in THF (5 mL) was added in dropwise and stirred at -78 °C for 10 min and then slowly warmed to 0 °C over 30 min under stirring. The reaction mixture was quenched with 10 % HCl solution, extracted with DCM, washed with brine, dried over Na2SO4, and concentrated to afford crude product was purified by silica gel (100-200 mesh) column chromatography, eluted with 30-40 % EtOAc in pet ether to afford the corresponding styryl pyrones.
56%	With magnesium methanolate Inert atmosphere; Reflux;	3.1.2 General procedure for the preparation of compounds 3-14 Compound 2 (2.40mmol) and appropriate aldehydes (2.40mmol) in the presence of Mg(OCH3)2 (10mL) was refluxed under N2 overnight. After the reaction was completed as indicated by TLC, the mixture was concentrated under reduced pressure. The residue was purified with silica gel chromatography to obtain target compounds 3-14. 3.1.2.1 (E)-4-methoxy-6-styryl-2H-pyran-2-one (3) Yield 56%; m.p. 147.2-149.3°C; white solid; 1H NMR (400MHz, CDCl3) δ 7.58 (d, J=7.1Hz, 2H), 7.44 (s, 1H), 7.37 (d, J=7.6Hz, 1H), 7.31 (s, 2H), 6.59 (dd, J=16.0, 4.1Hz, 1H), 5.95 (s, 1H), 5.50 (s, 1H), 3.82 (s, 3H).
53%	With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 25℃; for 48h;	Representative procedure General procedure: To a stirred solution of 4-methoxy-6-methyl-2-pyrone (0.067 g, 0.47 mmol) in DMF (1 mL) at room temperature was added benzaldehyde (0.1 mL, 0.95 mmol). Potassium tert-butoxide solid (0.1 g,0.95 mmol) was then added portionwise to it and stirred for 2 days at room temperature. Solution became dark red in color. This was extracted withdiethyl ether (3 10 mL). For the compounds 3, 4, 8, 9, 10 methylene chloridewas used for the extraction. The organic layer was washed with brine(3 20 mL), water (5 20 mL), dried over MgSO4, and concentrated in vacuo.The crude product was purified by preparative thin layer chromatography(EtOAc/hexanes) to afford the product.

49%	With magnesium methanolate In methanol at 60℃;	General procedure for the synthesis of compounds 1, 4-22, 27-29 General procedure: The synthesis of 5,6-dehydrokawain analogues were performed based on the method reported by McCracken, S. T. et al.2 Magnesium methoxide was prepared by gently heating Mg (156 mg) in anhydrous MeOH. 4-Methoxy-6-methyl-2-pyrone (3)3 (0.30 g, 2.1 mmol) or other 2-pyrones and each aldehyde (2.2 mmol) were added to the solution. The reaction mixture was heated at reflux for 3-6 hours, cooled, and dried in vacuo. The residual material was then suspended in acetic acid (3.3 M, 30 mL) and extracted with ethyl acetate for three times. The combined organic layer was washed with water and dried in vacuo. Purification of the compounds was conducted by preparative HPLC. NMR spectra were recorded on a JEOL JNM-ECZ400S in CDCl3. HRMS was recorded on a Thermo scientific Q Exactive instrument. Mp were recorded on a Yanagimoto micro melting point apparatus. The 1H and 13C NMR data observed for 11,4, 33, 73, 83, 105, 222, 256, 266 were agreed with those previously reported in the literature. The 1H NMR data of 247 and 278 were in agreement with literature values. (E)-4-Methoxy-6-styryl-2H-pyran-2-one (1) From pyrone (3.00 g, 21 mmol) and benzaldehyde (2.60 mL, 26 mmol). Yield: 49%. Mp 137-138 °C; HRMS (ESI): [M+H]+ calcd for C15H13O3, 229.0865; found, 229.0859. The 1H and 13C NMR data were in agreement with literature values.1,4
22%	With magnesium methanolate In methanol for 20h; Reflux; Inert atmosphere;	General Procedure for Preparation of Kavalactone Analogues 1-19. General procedure: Kavalactone analogues were prepared according to the previously reported method [24]. Amixture of 4-methoxy-6-methyl-pyran-2-one (25 mg, 0.178 mmol) and appropriate aldehyde (0.178mmol) in dimethoxymagnesium solution (60% in 2 mL methanol) was heated to reflux under anitrogen atmosphere for 20 h. After the reaction was completed, the mixture was concentrated underreduced pressure. The crude product was purified by flash column-chromatography (0%-40%EtOAc/cHexane) to give the title compound.

Reference： [1]Basu, Manas K.; Mukkanti, K.; Samala, Ramakrishna [Tetrahedron Letters, 2022, vol. 88]
[2]Li, Chanjuan; Cheng, Bao; Fang, Sai; Zhou, Huihao; Gu, Qiong; Xu, Jun [European Journal of Medicinal Chemistry, 2018, vol. 143, p. 114 - 122]
[3]Kraus, George A.; Wanninayake, Umayangani K. [Tetrahedron Letters, 2015, vol. 56, # 51, p. 7112 - 7114]
[4]Kumagai, Momochika; Nishikawa, Keisuke; Mishima, Takashi; Yoshida, Izumi; Ide, Masahiro; Koizumi, Keiko; Nakamura, Munetomo; Morimoto, Yoshiki [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 11, p. 2401 - 2406]
[5]Chang, Bill C. H.; Dilrukshi Herath, H. M. P.; Garcia-Bustos, José; Gasser, Robin B.; Hofmann, Andreas; Jabbar, Abdul; Ma, Guangxu; Nguyen, Nghi; Sleebs, Brad E.; Taki, Aya C.; Wang, Tao [Molecules, 2020, vol. 25, # 8]

35
[ 672-89-9 ]
[ 120-14-9 ]
4-methoxy-6-(2-(3,4-dimethoxyphenyl)ethenyl)-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
46%	With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 25℃; for 48h;	Representative procedure General procedure: To a stirred solution of 4-methoxy-6-methyl-2-pyrone (0.067 g, 0.47 mmol) in DMF (1 mL) at room temperature was added benzaldehyde (0.1 mL, 0.95 mmol). Potassium tert-butoxide solid (0.1 g,0.95 mmol) was then added portionwise to it and stirred for 2 days at room temperature. Solution became dark red in color. This was extracted withdiethyl ether (3 10 mL). For the compounds 3, 4, 8, 9, 10 methylene chloridewas used for the extraction. The organic layer was washed with brine(3 20 mL), water (5 20 mL), dried over MgSO4, and concentrated in vacuo.The crude product was purified by preparative thin layer chromatography(EtOAc/hexanes) to afford the product.

Reference： [1]Kraus, George A.; Wanninayake, Umayangani K. [Tetrahedron Letters, 2015, vol. 56, # 51, p. 7112 - 7114]

36
[ 672-89-9 ]
[ 5780-00-7 ]
(E)-4-methoxy-6-(2-(6-methoxybenzo[1,3]dioxol-5-yl)vinyl)-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 25℃; for 48h;	Representative procedure General procedure: To a stirred solution of 4-methoxy-6-methyl-2-pyrone (0.067 g, 0.47 mmol) in DMF (1 mL) at room temperature was added benzaldehyde (0.1 mL, 0.95 mmol). Potassium tert-butoxide solid (0.1 g,0.95 mmol) was then added portionwise to it and stirred for 2 days at room temperature. Solution became dark red in color. This was extracted withdiethyl ether (3 10 mL). For the compounds 3, 4, 8, 9, 10 methylene chloridewas used for the extraction. The organic layer was washed with brine(3 20 mL), water (5 20 mL), dried over MgSO4, and concentrated in vacuo.The crude product was purified by preparative thin layer chromatography(EtOAc/hexanes) to afford the product.

Reference： [1]Kraus, George A.; Wanninayake, Umayangani K. [Tetrahedron Letters, 2015, vol. 56, # 51, p. 7112 - 7114]

37
[ 672-89-9 ]
[ 555-16-8 ]
4-methoxy-6-(p-nitro-trans-styryl)-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
33%	With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 25℃; for 48h;	Representative procedure General procedure: To a stirred solution of 4-methoxy-6-methyl-2-pyrone (0.067 g, 0.47 mmol) in DMF (1 mL) at room temperature was added benzaldehyde (0.1 mL, 0.95 mmol). Potassium tert-butoxide solid (0.1 g,0.95 mmol) was then added portionwise to it and stirred for 2 days at room temperature. Solution became dark red in color. This was extracted withdiethyl ether (3 10 mL). For the compounds 3, 4, 8, 9, 10 methylene chloridewas used for the extraction. The organic layer was washed with brine(3 20 mL), water (5 20 mL), dried over MgSO4, and concentrated in vacuo.The crude product was purified by preparative thin layer chromatography(EtOAc/hexanes) to afford the product.

Reference： [1]Kraus, George A.; Wanninayake, Umayangani K. [Tetrahedron Letters, 2015, vol. 56, # 51, p. 7112 - 7114]

38
[ 672-89-9 ]
[ 2043-61-0 ]
6-[(E)-2-cyclohexylvinyl]-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With magnesium methanolate Inert atmosphere; Reflux;	3.1.2 General procedure for the preparation of compounds 3-14 General procedure: Compound 2 (2.40mmol) and appropriate aldehydes (2.40mmol) in the presence of Mg(OCH3)2 (10mL) was refluxed under N2 overnight. After the reaction was completed as indicated by TLC, the mixture was concentrated under reduced pressure. The residue was purified with silica gel chromatography to obtain target compounds 3-14.
31%	With magnesium methanolate In methanol at 60℃;	General procedure for the synthesis of compounds 1, 4-22, 27-29 General procedure: The synthesis of 5,6-dehydrokawain analogues were performed based on the method reported by McCracken, S. T. et al.2 Magnesium methoxide was prepared by gently heating Mg (156 mg) in anhydrous MeOH. 4-Methoxy-6-methyl-2-pyrone (3)3 (0.30 g, 2.1 mmol) or other 2-pyrones and each aldehyde (2.2 mmol) were added to the solution. The reaction mixture was heated at reflux for 3-6 hours, cooled, and dried in vacuo. The residual material was then suspended in acetic acid (3.3 M, 30 mL) and extracted with ethyl acetate for three times. The combined organic layer was washed with water and dried in vacuo. Purification of the compounds was conducted by preparative HPLC. NMR spectra were recorded on a JEOL JNM-ECZ400S in CDCl3. HRMS was recorded on a Thermo scientific Q Exactive instrument. Mp were recorded on a Yanagimoto micro melting point apparatus. The 1H and 13C NMR data observed for 11,4, 33, 73, 83, 105, 222, 256, 266 were agreed with those previously reported in the literature. The 1H NMR data of 247 and 278 were in agreement with literature values.
	With magnesium In methanol at 60℃; for 4h;	1 Compound 1: 6 - [(E) -2-Cyclohexylvinyl] -4-methoxy-2H-pyran-2-one (formula (1)) Metal Mg was heated in methanol (60 ° C.)And suspended. 4-methoxy-6-methyl-2-pyrone (0.30 g)And cyclohexanecarbaldehyde (0.27 ml, 2.2 mmol) were added,And heated at 60 ° C. for 4 hours. After cooling, acidifying with acetic acid,And extracted with ethyl acetate. After concentrating the extracted extract under reduced pressure,It was purified by reverse phase preparative HPLC (mobile phase: water-acetonitrile = 3: 7).

Reference： [1]Li, Chanjuan; Cheng, Bao; Fang, Sai; Zhou, Huihao; Gu, Qiong; Xu, Jun [European Journal of Medicinal Chemistry, 2018, vol. 143, p. 114 - 122]
[2]Kumagai, Momochika; Nishikawa, Keisuke; Mishima, Takashi; Yoshida, Izumi; Ide, Masahiro; Koizumi, Keiko; Nakamura, Munetomo; Morimoto, Yoshiki [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 11, p. 2401 - 2406]
[3]Current Patent Assignee: JAPAN FOOD RES LAB - JP2018/123111, 2018, A Location in patent: Paragraph 0035

39
[ 672-89-9 ]
[ 872-53-7 ]
6-[(E)-2-cyclopentylvinyl]-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
17%	With magnesium methanolate In methanol at 60℃;	General procedure for the synthesis of compounds 1, 4-22, 27-29 General procedure: The synthesis of 5,6-dehydrokawain analogues were performed based on the method reported by McCracken, S. T. et al.2 Magnesium methoxide was prepared by gently heating Mg (156 mg) in anhydrous MeOH. 4-Methoxy-6-methyl-2-pyrone (3)3 (0.30 g, 2.1 mmol) or other 2-pyrones and each aldehyde (2.2 mmol) were added to the solution. The reaction mixture was heated at reflux for 3-6 hours, cooled, and dried in vacuo. The residual material was then suspended in acetic acid (3.3 M, 30 mL) and extracted with ethyl acetate for three times. The combined organic layer was washed with water and dried in vacuo. Purification of the compounds was conducted by preparative HPLC. NMR spectra were recorded on a JEOL JNM-ECZ400S in CDCl3. HRMS was recorded on a Thermo scientific Q Exactive instrument. Mp were recorded on a Yanagimoto micro melting point apparatus. The 1H and 13C NMR data observed for 11,4, 33, 73, 83, 105, 222, 256, 266 were agreed with those previously reported in the literature. The 1H NMR data of 247 and 278 were in agreement with literature values.
17%	With magnesium In methanol at 60℃; for 5h;	1 Compound 15: 6 - [(E) -2-Cyclopentylvinyl] -4-methoxy-2H-pyran-2-one (formula (15)) Metal Mg was heated in methanol (60 ° C.) and suspended. 4-methoxy-6-methyl-2-pyrone (0.20 g) and cyclopentanecarboxaldehyde (0.24 ml, 2.2 mmol) were added thereto, and the mixture was heated at 60 ° C. for 5 hours. After cooling, it was acidified with acetic acid and extracted with ethyl acetate. The extract was concentrated under reduced pressure and then purified by reverse phase preparative HPLC (mobile phase: water-acetonitrile = 3: 7).Yield: 17%.

Reference： [1]Kumagai, Momochika; Nishikawa, Keisuke; Mishima, Takashi; Yoshida, Izumi; Ide, Masahiro; Koizumi, Keiko; Nakamura, Munetomo; Morimoto, Yoshiki [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 11, p. 2401 - 2406]
[2]Current Patent Assignee: JAPAN FOOD RES LAB - JP2018/123111, 2018, A Location in patent: Paragraph 0049

40
[ 672-89-9 ]
[ 1489-69-6 ]
6-[(E)-2-cyclopropylvinyl]-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
29%	With magnesium methanolate In methanol at 60℃;	General procedure for the synthesis of compounds 1, 4-22, 27-29 General procedure: The synthesis of 5,6-dehydrokawain analogues were performed based on the method reported by McCracken, S. T. et al.2 Magnesium methoxide was prepared by gently heating Mg (156 mg) in anhydrous MeOH. 4-Methoxy-6-methyl-2-pyrone (3)3 (0.30 g, 2.1 mmol) or other 2-pyrones and each aldehyde (2.2 mmol) were added to the solution. The reaction mixture was heated at reflux for 3-6 hours, cooled, and dried in vacuo. The residual material was then suspended in acetic acid (3.3 M, 30 mL) and extracted with ethyl acetate for three times. The combined organic layer was washed with water and dried in vacuo. Purification of the compounds was conducted by preparative HPLC. NMR spectra were recorded on a JEOL JNM-ECZ400S in CDCl3. HRMS was recorded on a Thermo scientific Q Exactive instrument. Mp were recorded on a Yanagimoto micro melting point apparatus. The 1H and 13C NMR data observed for 11,4, 33, 73, 83, 105, 222, 256, 266 were agreed with those previously reported in the literature. The 1H NMR data of 247 and 278 were in agreement with literature values.

Reference： [1]Kumagai, Momochika; Nishikawa, Keisuke; Mishima, Takashi; Yoshida, Izumi; Ide, Masahiro; Koizumi, Keiko; Nakamura, Munetomo; Morimoto, Yoshiki [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 11, p. 2401 - 2406]

41
[ 672-89-9 ]
[ 459-57-4 ]
[ 959273-94-0 ]

Yield	Reaction Conditions	Operation in experiment
20%	With magnesium methanolate In methanol at 60℃;	General procedure for the synthesis of compounds 1, 4-22, 27-29 General procedure: The synthesis of 5,6-dehydrokawain analogues were performed based on the method reported by McCracken, S. T. et al.2 Magnesium methoxide was prepared by gently heating Mg (156 mg) in anhydrous MeOH. 4-Methoxy-6-methyl-2-pyrone (3)3 (0.30 g, 2.1 mmol) or other 2-pyrones and each aldehyde (2.2 mmol) were added to the solution. The reaction mixture was heated at reflux for 3-6 hours, cooled, and dried in vacuo. The residual material was then suspended in acetic acid (3.3 M, 30 mL) and extracted with ethyl acetate for three times. The combined organic layer was washed with water and dried in vacuo. Purification of the compounds was conducted by preparative HPLC. NMR spectra were recorded on a JEOL JNM-ECZ400S in CDCl3. HRMS was recorded on a Thermo scientific Q Exactive instrument. Mp were recorded on a Yanagimoto micro melting point apparatus. The 1H and 13C NMR data observed for 11,4, 33, 73, 83, 105, 222, 256, 266 were agreed with those previously reported in the literature. The 1H NMR data of 247 and 278 were in agreement with literature values.

Reference： [1]Kumagai, Momochika; Nishikawa, Keisuke; Mishima, Takashi; Yoshida, Izumi; Ide, Masahiro; Koizumi, Keiko; Nakamura, Munetomo; Morimoto, Yoshiki [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 11, p. 2401 - 2406]

42
[ 672-89-9 ]
[ 104-88-1 ]
6-[(E)-2-(4-chlorophenyl)vinyl]-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	With magnesium methanolate Inert atmosphere; Reflux;	3.1.2 General procedure for the preparation of compounds 3-14 General procedure: Compound 2 (2.40mmol) and appropriate aldehydes (2.40mmol) in the presence of Mg(OCH3)2 (10mL) was refluxed under N2 overnight. After the reaction was completed as indicated by TLC, the mixture was concentrated under reduced pressure. The residue was purified with silica gel chromatography to obtain target compounds 3-14.
38%	With magnesium methanolate In methanol at 60℃;	General procedure for the synthesis of compounds 1, 4-22, 27-29 General procedure: The synthesis of 5,6-dehydrokawain analogues were performed based on the method reported by McCracken, S. T. et al.2 Magnesium methoxide was prepared by gently heating Mg (156 mg) in anhydrous MeOH. 4-Methoxy-6-methyl-2-pyrone (3)3 (0.30 g, 2.1 mmol) or other 2-pyrones and each aldehyde (2.2 mmol) were added to the solution. The reaction mixture was heated at reflux for 3-6 hours, cooled, and dried in vacuo. The residual material was then suspended in acetic acid (3.3 M, 30 mL) and extracted with ethyl acetate for three times. The combined organic layer was washed with water and dried in vacuo. Purification of the compounds was conducted by preparative HPLC. NMR spectra were recorded on a JEOL JNM-ECZ400S in CDCl3. HRMS was recorded on a Thermo scientific Q Exactive instrument. Mp were recorded on a Yanagimoto micro melting point apparatus. The 1H and 13C NMR data observed for 11,4, 33, 73, 83, 105, 222, 256, 266 were agreed with those previously reported in the literature. The 1H NMR data of 247 and 278 were in agreement with literature values.
14%	With magnesium methanolate In methanol for 20h; Reflux; Inert atmosphere;	General Procedure for Preparation of Kavalactone Analogues 1-19. General procedure: Kavalactone analogues were prepared according to the previously reported method [24]. Amixture of 4-methoxy-6-methyl-pyran-2-one (25 mg, 0.178 mmol) and appropriate aldehyde (0.178mmol) in dimethoxymagnesium solution (60% in 2 mL methanol) was heated to reflux under anitrogen atmosphere for 20 h. After the reaction was completed, the mixture was concentrated underreduced pressure. The crude product was purified by flash column-chromatography (0%-40%EtOAc/cHexane) to give the title compound.

With magnesium In methanol at 60℃; for 4h;

1 Compound 2: 6 - [(E) -2- (4-Chlorophenyl) vinyl] -4-methoxy- 2 H-pyran-2-one (formula (2)) Metal Mg was heated in methanol (60 ° C.) and suspended. 4-methoxy-6-methyl-2-pyrone (0.20 g) and 4-chlorobenzaldehyde (0.23 g, 1.6 mmol) were added thereto, and the mixture was heated at 60 ° C. for 4 hours. After cooling, it was acidified with acetic acid and extracted with ethyl acetate. The extract was concentrated under reduced pressure and then purified by reverse phase preparative HPLC (mobile phase: water-acetonitrile = 3: 7).

Reference： [1]Li, Chanjuan; Cheng, Bao; Fang, Sai; Zhou, Huihao; Gu, Qiong; Xu, Jun [European Journal of Medicinal Chemistry, 2018, vol. 143, p. 114 - 122]
[2]Kumagai, Momochika; Nishikawa, Keisuke; Mishima, Takashi; Yoshida, Izumi; Ide, Masahiro; Koizumi, Keiko; Nakamura, Munetomo; Morimoto, Yoshiki [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 11, p. 2401 - 2406]
[3]Chang, Bill C. H.; Dilrukshi Herath, H. M. P.; Garcia-Bustos, José; Gasser, Robin B.; Hofmann, Andreas; Jabbar, Abdul; Ma, Guangxu; Nguyen, Nghi; Sleebs, Brad E.; Taki, Aya C.; Wang, Tao [Molecules, 2020, vol. 25, # 8]
[4]Current Patent Assignee: JAPAN FOOD RES LAB - JP2018/123111, 2018, A Location in patent: Paragraph 0036

43
[ 672-89-9 ]
[ 10031-82-0 ]
6-[(E)-2-(4-ethoxyphenyl)vinyl]-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
26%	With magnesium methanolate In methanol at 60℃;	General procedure for the synthesis of compounds 1, 4-22, 27-29 General procedure: The synthesis of 5,6-dehydrokawain analogues were performed based on the method reported by McCracken, S. T. et al.2 Magnesium methoxide was prepared by gently heating Mg (156 mg) in anhydrous MeOH. 4-Methoxy-6-methyl-2-pyrone (3)3 (0.30 g, 2.1 mmol) or other 2-pyrones and each aldehyde (2.2 mmol) were added to the solution. The reaction mixture was heated at reflux for 3-6 hours, cooled, and dried in vacuo. The residual material was then suspended in acetic acid (3.3 M, 30 mL) and extracted with ethyl acetate for three times. The combined organic layer was washed with water and dried in vacuo. Purification of the compounds was conducted by preparative HPLC. NMR spectra were recorded on a JEOL JNM-ECZ400S in CDCl3. HRMS was recorded on a Thermo scientific Q Exactive instrument. Mp were recorded on a Yanagimoto micro melting point apparatus. The 1H and 13C NMR data observed for 11,4, 33, 73, 83, 105, 222, 256, 266 were agreed with those previously reported in the literature. The 1H NMR data of 247 and 278 were in agreement with literature values.
	With magnesium In methanol at 60℃; for 4h;	1 Compound 3: 6 - [(E) -2- (4-Ethoxyphenyl) vinyl] -4-methoxy- 2 H-pyran-2-one (formula (3)) Metal Mg was heated in methanol (60 ° C.) and suspended. 4-methoxy-6-methyl-2-pyrone (0.20 g) and 4-ethoxybenzaldehyde (0.22 ml, 1.6 mmol) were added thereto, and the mixture was heated at 60 ° C. for 4 hours. After cooling, it was acidified with acetic acid and extracted with ethyl acetate. The extract was concentrated under reduced pressure and then purified by reverse phase preparative HPLC (mobile phase: water-acetonitrile = 3: 7).

Reference： [1]Kumagai, Momochika; Nishikawa, Keisuke; Mishima, Takashi; Yoshida, Izumi; Ide, Masahiro; Koizumi, Keiko; Nakamura, Munetomo; Morimoto, Yoshiki [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 11, p. 2401 - 2406]
[2]Current Patent Assignee: JAPAN FOOD RES LAB - JP2018/123111, 2018, A Location in patent: Paragraph 0037

44
[ 455-19-6 ]
[ 672-89-9 ]
4-methoxy-6-[(E)-2-(4-trifluoromethylphenyl)vinyl]-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	With magnesium methanolate In methanol at 60℃;	General procedure for the synthesis of compounds 1, 4-22, 27-29 General procedure: The synthesis of 5,6-dehydrokawain analogues were performed based on the method reported by McCracken, S. T. et al.2 Magnesium methoxide was prepared by gently heating Mg (156 mg) in anhydrous MeOH. 4-Methoxy-6-methyl-2-pyrone (3)3 (0.30 g, 2.1 mmol) or other 2-pyrones and each aldehyde (2.2 mmol) were added to the solution. The reaction mixture was heated at reflux for 3-6 hours, cooled, and dried in vacuo. The residual material was then suspended in acetic acid (3.3 M, 30 mL) and extracted with ethyl acetate for three times. The combined organic layer was washed with water and dried in vacuo. Purification of the compounds was conducted by preparative HPLC. NMR spectra were recorded on a JEOL JNM-ECZ400S in CDCl3. HRMS was recorded on a Thermo scientific Q Exactive instrument. Mp were recorded on a Yanagimoto micro melting point apparatus. The 1H and 13C NMR data observed for 11,4, 33, 73, 83, 105, 222, 256, 266 were agreed with those previously reported in the literature. The 1H NMR data of 247 and 278 were in agreement with literature values.
25%	With magnesium In methanol at 60℃;	1 Compound 13: 4-Methoxy-6 - [(E) -2- (4-trifluoromethylphenyl) vinyl] -2H-pyran-2-one (formula (13)) Metal Mg was heated in methanol (60 ° C.) and suspended. 4-Methoxy-6-methyl-2-pyrone (0.20 g) and 4-trifluoromethylbenzaldehyde (0.22 ml, 1.6 mmol) were added thereto, and the mixture was heated at 60 ° C. for a period of time. After cooling, it was acidified with acetic acid and extracted with ethyl acetate. The extract was concentrated under reduced pressure and then purified by reverse phase preparative HPLC (mobile phase: water-acetonitrile = 3: 7).Yield: 25%.
23%	With magnesium methanolate In methanol for 20h; Reflux; Inert atmosphere;	General Procedure for Preparation of Kavalactone Analogues 1-19. General procedure: Kavalactone analogues were prepared according to the previously reported method [24]. Amixture of 4-methoxy-6-methyl-pyran-2-one (25 mg, 0.178 mmol) and appropriate aldehyde (0.178mmol) in dimethoxymagnesium solution (60% in 2 mL methanol) was heated to reflux under anitrogen atmosphere for 20 h. After the reaction was completed, the mixture was concentrated underreduced pressure. The crude product was purified by flash column-chromatography (0%-40%EtOAc/cHexane) to give the title compound.

Reference： [1]Kumagai, Momochika; Nishikawa, Keisuke; Mishima, Takashi; Yoshida, Izumi; Ide, Masahiro; Koizumi, Keiko; Nakamura, Munetomo; Morimoto, Yoshiki [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 11, p. 2401 - 2406]
[2]Current Patent Assignee: JAPAN FOOD RES LAB - JP2018/123111, 2018, A Location in patent: Paragraph 0047
[3]Chang, Bill C. H.; Dilrukshi Herath, H. M. P.; Garcia-Bustos, José; Gasser, Robin B.; Hofmann, Andreas; Jabbar, Abdul; Ma, Guangxu; Nguyen, Nghi; Sleebs, Brad E.; Taki, Aya C.; Wang, Tao [Molecules, 2020, vol. 25, # 8]

45
[ 498-62-4 ]
[ 672-89-9 ]
4-methoxy-6-[(E)-2-thiophen-3-ylvinyl]-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	With magnesium methanolate In methanol at 60℃;	General procedure for the synthesis of compounds 1, 4-22, 27-29 General procedure: The synthesis of 5,6-dehydrokawain analogues were performed based on the method reported by McCracken, S. T. et al.2 Magnesium methoxide was prepared by gently heating Mg (156 mg) in anhydrous MeOH. 4-Methoxy-6-methyl-2-pyrone (3)3 (0.30 g, 2.1 mmol) or other 2-pyrones and each aldehyde (2.2 mmol) were added to the solution. The reaction mixture was heated at reflux for 3-6 hours, cooled, and dried in vacuo. The residual material was then suspended in acetic acid (3.3 M, 30 mL) and extracted with ethyl acetate for three times. The combined organic layer was washed with water and dried in vacuo. Purification of the compounds was conducted by preparative HPLC. NMR spectra were recorded on a JEOL JNM-ECZ400S in CDCl3. HRMS was recorded on a Thermo scientific Q Exactive instrument. Mp were recorded on a Yanagimoto micro melting point apparatus. The 1H and 13C NMR data observed for 11,4, 33, 73, 83, 105, 222, 256, 266 were agreed with those previously reported in the literature. The 1H NMR data of 247 and 278 were in agreement with literature values.
40%	With magnesium In methanol at 60℃; for 5h;	1 Compound 16: 4-Methoxy-6 - [(E) -2-thiophen-3-ylvinyl] -2H-pyran-2-one (formula (16)) Metal Mg was heated in methanol (60 ° C.) and suspended. 4-methoxy-6-methyl-2-pyrone (0.20 g) and 3-thiophencarbox aldehyde (0.15 ml, 1.6 mmol) were added thereto, and the mixture was heated at 60 ° C. for 5 hours. After cooling, it was acidified with acetic acid and extracted with ethyl acetate. The extract was concentrated under reduced pressure and then purified by reverse phase preparative HPLC (mobile phase: water-acetonitrile = 3: 7).Yield: 40%.

Reference： [1]Kumagai, Momochika; Nishikawa, Keisuke; Mishima, Takashi; Yoshida, Izumi; Ide, Masahiro; Koizumi, Keiko; Nakamura, Munetomo; Morimoto, Yoshiki [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 11, p. 2401 - 2406]
[2]Current Patent Assignee: JAPAN FOOD RES LAB - JP2018/123111, 2018, A Location in patent: Paragraph 0050

46
[ 672-89-9 ]
[ 63697-96-1 ]
6-[(E)-2-(4-ethynylphenyl)vinyl]-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	With magnesium methanolate In methanol at 60℃;	General procedure for the synthesis of compounds 1, 4-22, 27-29 General procedure: The synthesis of 5,6-dehydrokawain analogues were performed based on the method reported by McCracken, S. T. et al.2 Magnesium methoxide was prepared by gently heating Mg (156 mg) in anhydrous MeOH. 4-Methoxy-6-methyl-2-pyrone (3)3 (0.30 g, 2.1 mmol) or other 2-pyrones and each aldehyde (2.2 mmol) were added to the solution. The reaction mixture was heated at reflux for 3-6 hours, cooled, and dried in vacuo. The residual material was then suspended in acetic acid (3.3 M, 30 mL) and extracted with ethyl acetate for three times. The combined organic layer was washed with water and dried in vacuo. Purification of the compounds was conducted by preparative HPLC. NMR spectra were recorded on a JEOL JNM-ECZ400S in CDCl3. HRMS was recorded on a Thermo scientific Q Exactive instrument. Mp were recorded on a Yanagimoto micro melting point apparatus. The 1H and 13C NMR data observed for 11,4, 33, 73, 83, 105, 222, 256, 266 were agreed with those previously reported in the literature. The 1H NMR data of 247 and 278 were in agreement with literature values.
	With magnesium In methanol at 60℃; for 5h;	1 Compound 4: 6 - [(E) -2- (4-Ethynylphenyl) vinyl] -4-methoxy- 2 H-pyran-2-one (formula (4)) Metal Mg was heated in methanol (60 ° C.) and suspended. 4-methoxy-6-methyl-2-pyrone (0.20 g) and 4-ethinylbenzaldehyde (0.21 g, 1.6 mmol) were added thereto, and the mixture was heated at 60 ° C. for 5 hours. After cooling, it was acidified with acetic acid and extracted with ethyl acetate. The extract was concentrated under reduced pressure and then purified by reverse phase preparative HPLC (mobile phase: water-acetonitrile = 3: 7).

Reference： [1]Kumagai, Momochika; Nishikawa, Keisuke; Mishima, Takashi; Yoshida, Izumi; Ide, Masahiro; Koizumi, Keiko; Nakamura, Munetomo; Morimoto, Yoshiki [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 11, p. 2401 - 2406]
[2]Current Patent Assignee: JAPAN FOOD RES LAB - JP2018/123111, 2018, A Location in patent: Paragraph 0038

47
[ 672-89-9 ]
[ 4748-78-1 ]
6-[(E)-2-(4-ethylphenyl)vinyl]-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
34%	With magnesium methanolate In methanol at 60℃;	General procedure for the synthesis of compounds 1, 4-22, 27-29 General procedure: The synthesis of 5,6-dehydrokawain analogues were performed based on the method reported by McCracken, S. T. et al.2 Magnesium methoxide was prepared by gently heating Mg (156 mg) in anhydrous MeOH. 4-Methoxy-6-methyl-2-pyrone (3)3 (0.30 g, 2.1 mmol) or other 2-pyrones and each aldehyde (2.2 mmol) were added to the solution. The reaction mixture was heated at reflux for 3-6 hours, cooled, and dried in vacuo. The residual material was then suspended in acetic acid (3.3 M, 30 mL) and extracted with ethyl acetate for three times. The combined organic layer was washed with water and dried in vacuo. Purification of the compounds was conducted by preparative HPLC. NMR spectra were recorded on a JEOL JNM-ECZ400S in CDCl3. HRMS was recorded on a Thermo scientific Q Exactive instrument. Mp were recorded on a Yanagimoto micro melting point apparatus. The 1H and 13C NMR data observed for 11,4, 33, 73, 83, 105, 222, 256, 266 were agreed with those previously reported in the literature. The 1H NMR data of 247 and 278 were in agreement with literature values.
	With magnesium In methanol at 60℃; for 5h;	1 Compound 6: 6 - [(E) -2- (4-Ethylphenyl) vinyl] -4-methoxy- 2 H-pyran-2-one (formula (6)) Metal Mg was heated in methanol (60 ° C.) and suspended. 4-methoxy-6-methyl-2-pyrone (0.20 g) and 4-ethylbenzaldehyde (0.21 ml, 1.6 mmol) were added thereto, and the mixture was heated at 60 ° C. for 5 hours. After cooling, it was acidified with acetic acid and extracted with ethyl acetate. The extract was concentrated under reduced pressure and then purified by reverse phase preparative HPLC (mobile phase: water-acetonitrile = 3: 7).

Reference： [1]Kumagai, Momochika; Nishikawa, Keisuke; Mishima, Takashi; Yoshida, Izumi; Ide, Masahiro; Koizumi, Keiko; Nakamura, Munetomo; Morimoto, Yoshiki [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 11, p. 2401 - 2406]
[2]Current Patent Assignee: JAPAN FOOD RES LAB - JP2018/123111, 2018, A Location in patent: Paragraph 0040

48
[ 672-89-9 ]
[ 34246-54-3 ]
6-[(E)-2-(3-ethylphenyl)vinyl]-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32%	With magnesium methanolate; In methanol; at 60℃;	General procedure: The synthesis of 5,6-dehydrokawain analogues were performed based on the method reported by McCracken, S. T. et al.2 Magnesium methoxide was prepared by gently heating Mg (156 mg) in anhydrous MeOH. 4-Methoxy-6-methyl-2-pyrone (3)3 (0.30 g, 2.1 mmol) or other 2-pyrones and each aldehyde (2.2 mmol) were added to the solution. The reaction mixture was heated at reflux for 3-6 hours, cooled, and dried in vacuo. The residual material was then suspended in acetic acid (3.3 M, 30 mL) and extracted with ethyl acetate for three times. The combined organic layer was washed with water and dried in vacuo. Purification of the compounds was conducted by preparative HPLC. NMR spectra were recorded on a JEOL JNM-ECZ400S in CDCl3. HRMS was recorded on a Thermo scientific Q Exactive instrument. Mp were recorded on a Yanagimoto micro melting point apparatus. The 1H and 13C NMR data observed for 11,4, 33, 73, 83, 105, 222, 256, 266 were agreed with those previously reported in the literature. The 1H NMR data of 247 and 278 were in agreement with literature values.
32%	With magnesium; In methanol; at 60℃; for 6h;	Metal Mg was heated in methanol (60 C.) and suspended. 4-methoxy-6-methyl-2-pyrone (0.20 g) and <strong>[34246-54-3]3-ethylbenzaldehyde</strong> (0.21 ml, 1.6 mmol) were added thereto, and the mixture was heated at 60 C. for 6 hours. After cooling, it was acidified with acetic acid and extracted with ethyl acetate. The extract was concentrated under reduced pressure and then purified by reverse phase preparative HPLC (mobile phase: water-acetonitrile = 3: 7).Yield: 32%.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2401 - 2406
[2]Patent: JP2018/123111,2018,A .Location in patent: Paragraph 0045

49
[ 672-89-9 ]
[ 22927-13-5 ]
6-[(E)-2-(2-ethylphenyl)vinyl]-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	With magnesium methanolate; In methanol; at 60℃;	General procedure: The synthesis of 5,6-dehydrokawain analogues were performed based on the method reported by McCracken, S. T. et al.2 Magnesium methoxide was prepared by gently heating Mg (156 mg) in anhydrous MeOH. 4-Methoxy-6-methyl-2-pyrone (3)3 (0.30 g, 2.1 mmol) or other 2-pyrones and each aldehyde (2.2 mmol) were added to the solution. The reaction mixture was heated at reflux for 3-6 hours, cooled, and dried in vacuo. The residual material was then suspended in acetic acid (3.3 M, 30 mL) and extracted with ethyl acetate for three times. The combined organic layer was washed with water and dried in vacuo. Purification of the compounds was conducted by preparative HPLC. NMR spectra were recorded on a JEOL JNM-ECZ400S in CDCl3. HRMS was recorded on a Thermo scientific Q Exactive instrument. Mp were recorded on a Yanagimoto micro melting point apparatus. The 1H and 13C NMR data observed for 11,4, 33, 73, 83, 105, 222, 256, 266 were agreed with those previously reported in the literature. The 1H NMR data of 247 and 278 were in agreement with literature values.
35%	With magnesium; In methanol; at 60℃; for 5h;	Metal Mg was heated in methanol (60 C.) and suspended. 4-methoxy-6-methyl-2-pyrone (0.20 g) and <strong>[22927-13-5]2-ethylbenzaldehyde</strong> (0.21 ml, 1.6 mmol) were added thereto, and the mixture was heated at 60 C. for 5 hours. After cooling, it was acidified with acetic acid and extracted with ethyl acetate. The extract was concentrated under reduced pressure and then purified by reverse phase preparative HPLC (mobile phase: water-acetonitrile = 3: 7).Yield: 35%

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2401 - 2406
[2]Patent: JP2018/123111,2018,A .Location in patent: Paragraph 0046

50
[ 672-89-9 ]
[ 104-87-0 ]
(E)-4-methoxy-6-(4-methylstyryl)-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	Stage #1: 4-methoxy-6-methyl-2H-pyran-2-one With potassium hexamethylsilazane In tetrahydrofuran at -78℃; for 0.166667h; Inert atmosphere; Stage #2: 4-methyl-benzaldehyde In tetrahydrofuran at -78 - 0℃; for 0.666667h; Inert atmosphere; stereoselective reaction;	General Procedure for the synthesis of (E)-4-methoxy-6-styryl-2H-pyran-2-one using KHMDS General procedure: To a solution of Pyrone (1.0 mmol, 1.0 equiv.) in THF (10 mL) was added KHMDS (1M in THF, 1.6 mmol, 1.6 equiv.) at -78 °C under nitrogen and stirred for 10 min, and then aldehyde (1.6 mmol, 1.6 equiv.) in THF (5 mL) was added in dropwise and stirred at -78 °C for 10 min and then slowly warmed to 0 °C over 30 min under stirring. The reaction mixture was quenched with 10 % HCl solution, extracted with DCM, washed with brine, dried over Na2SO4, and concentrated to afford crude product was purified by silica gel (100-200 mesh) column chromatography, eluted with 30-40 % EtOAc in pet ether to afford the corresponding styryl pyrones.
23%	With magnesium methanolate In methanol for 20h; Reflux; Inert atmosphere;	General Procedure for Preparation of Kavalactone Analogues 1-19. General procedure: Kavalactone analogues were prepared according to the previously reported method [24]. Amixture of 4-methoxy-6-methyl-pyran-2-one (25 mg, 0.178 mmol) and appropriate aldehyde (0.178mmol) in dimethoxymagnesium solution (60% in 2 mL methanol) was heated to reflux under anitrogen atmosphere for 20 h. After the reaction was completed, the mixture was concentrated underreduced pressure. The crude product was purified by flash column-chromatography (0%-40%EtOAc/cHexane) to give the title compound.
14%	With magnesium methanolate In methanol at 60℃;	General procedure for the synthesis of compounds 1, 4-22, 27-29 General procedure: The synthesis of 5,6-dehydrokawain analogues were performed based on the method reported by McCracken, S. T. et al.2 Magnesium methoxide was prepared by gently heating Mg (156 mg) in anhydrous MeOH. 4-Methoxy-6-methyl-2-pyrone (3)3 (0.30 g, 2.1 mmol) or other 2-pyrones and each aldehyde (2.2 mmol) were added to the solution. The reaction mixture was heated at reflux for 3-6 hours, cooled, and dried in vacuo. The residual material was then suspended in acetic acid (3.3 M, 30 mL) and extracted with ethyl acetate for three times. The combined organic layer was washed with water and dried in vacuo. Purification of the compounds was conducted by preparative HPLC. NMR spectra were recorded on a JEOL JNM-ECZ400S in CDCl3. HRMS was recorded on a Thermo scientific Q Exactive instrument. Mp were recorded on a Yanagimoto micro melting point apparatus. The 1H and 13C NMR data observed for 11,4, 33, 73, 83, 105, 222, 256, 266 were agreed with those previously reported in the literature. The 1H NMR data of 247 and 278 were in agreement with literature values.

With magnesium In methanol at 60℃; for 6h;

1 Compound 5: 4-Methoxy-6 - [(E) -2-p-tolylvinyl] -2H-pyran-2-one (formula (5)) Metal Mg was heated in methanol (60 ° C.) and suspended. 4-methoxy-6-methyl-2-pyrone (0.20 g) and 4-methylbenzaldehyde (0.18 ml, 1.6 mmol) were added thereto, and the mixture was heated at 60 ° C. for 6 hours. After cooling, it was acidified with acetic acid and extracted with ethyl acetate. The extract was concentrated under reduced pressure and then purified by reverse phase preparative HPLC (mobile phase: water-acetonitrile = 3: 7).

Reference： [1]Basu, Manas K.; Mukkanti, K.; Samala, Ramakrishna [Tetrahedron Letters, 2022, vol. 88]
[2]Chang, Bill C. H.; Dilrukshi Herath, H. M. P.; Garcia-Bustos, José; Gasser, Robin B.; Hofmann, Andreas; Jabbar, Abdul; Ma, Guangxu; Nguyen, Nghi; Sleebs, Brad E.; Taki, Aya C.; Wang, Tao [Molecules, 2020, vol. 25, # 8]
[3]Kumagai, Momochika; Nishikawa, Keisuke; Mishima, Takashi; Yoshida, Izumi; Ide, Masahiro; Koizumi, Keiko; Nakamura, Munetomo; Morimoto, Yoshiki [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 11, p. 2401 - 2406]
[4]Current Patent Assignee: JAPAN FOOD RES LAB - JP2018/123111, 2018, A Location in patent: Paragraph 0039

51
[ 672-89-9 ]
[ 620-23-5 ]
(E)-4-methoxy-6-(3-methylstyryl)-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
33%	With magnesium methanolate In methanol at 60℃;	General procedure for the synthesis of compounds 1, 4-22, 27-29 General procedure: The synthesis of 5,6-dehydrokawain analogues were performed based on the method reported by McCracken, S. T. et al.2 Magnesium methoxide was prepared by gently heating Mg (156 mg) in anhydrous MeOH. 4-Methoxy-6-methyl-2-pyrone (3)3 (0.30 g, 2.1 mmol) or other 2-pyrones and each aldehyde (2.2 mmol) were added to the solution. The reaction mixture was heated at reflux for 3-6 hours, cooled, and dried in vacuo. The residual material was then suspended in acetic acid (3.3 M, 30 mL) and extracted with ethyl acetate for three times. The combined organic layer was washed with water and dried in vacuo. Purification of the compounds was conducted by preparative HPLC. NMR spectra were recorded on a JEOL JNM-ECZ400S in CDCl3. HRMS was recorded on a Thermo scientific Q Exactive instrument. Mp were recorded on a Yanagimoto micro melting point apparatus. The 1H and 13C NMR data observed for 11,4, 33, 73, 83, 105, 222, 256, 266 were agreed with those previously reported in the literature. The 1H NMR data of 247 and 278 were in agreement with literature values.
	With magnesium In methanol at 60℃; for 6h;	1 Compound 9: 4-Methoxy-6 - [(E) -2-m-tolylvinyl] -2H-pyran-2-one (formula (9)) Metal Mg was heated in methanol (60 ° C.) and suspended. 4-methoxy-6-methyl-2-pyrone (0.20 g) and 3-methylbenzaldehyde (0.18 ml, 1.6 mmol) were added thereto, and the mixture was heated at 60 ° C. for 6 hours. After cooling, it was acidified with acetic acid and extracted with ethyl acetate. The extract was concentrated under reduced pressure and then purified by reverse phase preparative HPLC (mobile phase: water-acetonitrile = 3: 7).

Reference： [1]Kumagai, Momochika; Nishikawa, Keisuke; Mishima, Takashi; Yoshida, Izumi; Ide, Masahiro; Koizumi, Keiko; Nakamura, Munetomo; Morimoto, Yoshiki [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 11, p. 2401 - 2406]
[2]Current Patent Assignee: JAPAN FOOD RES LAB - JP2018/123111, 2018, A Location in patent: Paragraph 0043

52
[ 672-89-9 ]
[ 529-20-4 ]
(E)-4-methoxy-6-(2-methylstyryl)-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30%	With magnesium methanolate In methanol at 60℃;	General procedure for the synthesis of compounds 1, 4-22, 27-29 General procedure: The synthesis of 5,6-dehydrokawain analogues were performed based on the method reported by McCracken, S. T. et al.2 Magnesium methoxide was prepared by gently heating Mg (156 mg) in anhydrous MeOH. 4-Methoxy-6-methyl-2-pyrone (3)3 (0.30 g, 2.1 mmol) or other 2-pyrones and each aldehyde (2.2 mmol) were added to the solution. The reaction mixture was heated at reflux for 3-6 hours, cooled, and dried in vacuo. The residual material was then suspended in acetic acid (3.3 M, 30 mL) and extracted with ethyl acetate for three times. The combined organic layer was washed with water and dried in vacuo. Purification of the compounds was conducted by preparative HPLC. NMR spectra were recorded on a JEOL JNM-ECZ400S in CDCl3. HRMS was recorded on a Thermo scientific Q Exactive instrument. Mp were recorded on a Yanagimoto micro melting point apparatus. The 1H and 13C NMR data observed for 11,4, 33, 73, 83, 105, 222, 256, 266 were agreed with those previously reported in the literature. The 1H NMR data of 247 and 278 were in agreement with literature values.
	With magnesium In methanol at 60℃; for 6h;	1 Compound 10: 4-Methoxy-6 - [(E) -2-o-tolylvinyl] -2H-pyran-2-one (formula (10)) Metal Mg was heated in methanol (60 ° C.) and suspended. 4-methoxy-6-methyl-2-pyrone (0.20 g) and 2-methylbenzaldehyde (0.18 ml, 1.6 mmol) were added thereto, and the mixture was heated at 60 ° C. for 6 hours. After cooling, it was acidified with acetic acid and extracted with ethyl acetate. The extract was concentrated under reduced pressure and then purified by reverse phase preparative HPLC (mobile phase: water-acetonitrile = 3: 7).
	With magnesium In methanol at 60℃; for 6h;	1 Compound 17: 6 - [(E) -2- (4-Fluorophenyl) vinyl] -4-methoxy- 2 H-pyran-2-one (formula (17)) Metal Mg was heated in methanol (60 ° C.) and suspended. 4-methoxy-6-methyl-2-pyrone (0.30 g) and 4-fluorobenzaldehyde (0.24 ml, 2.2 mmol) were added thereto, and the mixture was heated at 60 ° C. for 5 hours. After cooling, it was acidified with acetic acid and extracted with ethyl acetate. The extract was concentrated under reduced pressure and then purified by reverse phase preparative HPLC (mobile phase: water-acetonitrile = 3: 7).Yield: 20%.

Reference： [1]Kumagai, Momochika; Nishikawa, Keisuke; Mishima, Takashi; Yoshida, Izumi; Ide, Masahiro; Koizumi, Keiko; Nakamura, Munetomo; Morimoto, Yoshiki [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 11, p. 2401 - 2406]
[2]Current Patent Assignee: JAPAN FOOD RES LAB - JP2018/123111, 2018, A Location in patent: Paragraph 0044
[3]Current Patent Assignee: JAPAN FOOD RES LAB - JP2018/123111, 2018, A Location in patent: Paragraph 0051

53
[ 672-89-9 ]
[ 28785-06-0 ]
4-methoxy-6-[(E)-2-(4-propylphenyl)vinyl]-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
23%	With magnesium methanolate; In methanol; at 60℃;	General procedure: The synthesis of 5,6-dehydrokawain analogues were performed based on the method reported by McCracken, S. T. et al.2 Magnesium methoxide was prepared by gently heating Mg (156 mg) in anhydrous MeOH. 4-Methoxy-6-methyl-2-pyrone (3)3 (0.30 g, 2.1 mmol) or other 2-pyrones and each aldehyde (2.2 mmol) were added to the solution. The reaction mixture was heated at reflux for 3-6 hours, cooled, and dried in vacuo. The residual material was then suspended in acetic acid (3.3 M, 30 mL) and extracted with ethyl acetate for three times. The combined organic layer was washed with water and dried in vacuo. Purification of the compounds was conducted by preparative HPLC. NMR spectra were recorded on a JEOL JNM-ECZ400S in CDCl3. HRMS was recorded on a Thermo scientific Q Exactive? instrument. Mp were recorded on a Yanagimoto micro melting point apparatus. The 1H and 13C NMR data observed for 11,4, 33, 73, 83, 105, 222, 256, 266 were agreed with those previously reported in the literature. The 1H NMR data of 247 and 278 were in agreement with literature values.
	With magnesium; In methanol; at 60℃; for 5h;	Metal Mg was heated in methanol (60 ° C.) and suspended. 4-methoxy-6-methyl-2-pyrone (0.30 g) and <strong>[28785-06-0]4-propylbenzaldehyde</strong> (0.32 ml, 2.2 mmol) were added thereto, and the mixture was heated at 60 ° C. for 5 hours. After cooling, it was acidified with acetic acid and extracted with ethyl acetate. The extract was concentrated under reduced pressure and then purified by reverse phase preparative HPLC (mobile phase: water-acetonitrile = 3: 7).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2401 - 2406
[2]Patent: JP2018/123111,2018,A .Location in patent: Paragraph 0041

54
[ 672-89-9 ]
[ 1200-14-2 ]
6-[(E)-2-(4-butylphenyl)vinyl]-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
22%	With magnesium methanolate In methanol at 60℃;	General procedure for the synthesis of compounds 1, 4-22, 27-29 General procedure: The synthesis of 5,6-dehydrokawain analogues were performed based on the method reported by McCracken, S. T. et al.2 Magnesium methoxide was prepared by gently heating Mg (156 mg) in anhydrous MeOH. 4-Methoxy-6-methyl-2-pyrone (3)3 (0.30 g, 2.1 mmol) or other 2-pyrones and each aldehyde (2.2 mmol) were added to the solution. The reaction mixture was heated at reflux for 3-6 hours, cooled, and dried in vacuo. The residual material was then suspended in acetic acid (3.3 M, 30 mL) and extracted with ethyl acetate for three times. The combined organic layer was washed with water and dried in vacuo. Purification of the compounds was conducted by preparative HPLC. NMR spectra were recorded on a JEOL JNM-ECZ400S in CDCl3. HRMS was recorded on a Thermo scientific Q Exactive instrument. Mp were recorded on a Yanagimoto micro melting point apparatus. The 1H and 13C NMR data observed for 11,4, 33, 73, 83, 105, 222, 256, 266 were agreed with those previously reported in the literature. The 1H NMR data of 247 and 278 were in agreement with literature values.
	With magnesium In methanol at 60℃; for 4h;	1 Compound 8: 6 - [(E) -2- (4-Butylphenyl) vinyl] -4-methoxy- 2 H-pyran-2-one (formula (8)) Metal Mg was heated in methanol (60 ° C.) and suspended. 4-methoxy-6-methyl-2-pyrone (0.20 g) and 4-butylbenzaldehyde (0.41 ml, 1.6 mmol) were added thereto, and the mixture was heated at 60 ° C. for 4 hours. After cooling, it was acidified with acetic acid and extracted with ethyl acetate. The extract was concentrated under reduced pressure and then purified by reverse phase preparative HPLC (mobile phase: water-acetonitrile = 3: 7).

Reference： [1]Kumagai, Momochika; Nishikawa, Keisuke; Mishima, Takashi; Yoshida, Izumi; Ide, Masahiro; Koizumi, Keiko; Nakamura, Munetomo; Morimoto, Yoshiki [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 11, p. 2401 - 2406]
[2]Current Patent Assignee: JAPAN FOOD RES LAB - JP2018/123111, 2018, A Location in patent: Paragraph 0042

55
[ 672-89-9 ]
[ 939-97-9 ]
6-[(E)-2-(4-tert-butylphenyl)vinyl]-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
26%	With magnesium methanolate In methanol at 60℃;	General procedure for the synthesis of compounds 1, 4-22, 27-29 General procedure: The synthesis of 5,6-dehydrokawain analogues were performed based on the method reported by McCracken, S. T. et al.2 Magnesium methoxide was prepared by gently heating Mg (156 mg) in anhydrous MeOH. 4-Methoxy-6-methyl-2-pyrone (3)3 (0.30 g, 2.1 mmol) or other 2-pyrones and each aldehyde (2.2 mmol) were added to the solution. The reaction mixture was heated at reflux for 3-6 hours, cooled, and dried in vacuo. The residual material was then suspended in acetic acid (3.3 M, 30 mL) and extracted with ethyl acetate for three times. The combined organic layer was washed with water and dried in vacuo. Purification of the compounds was conducted by preparative HPLC. NMR spectra were recorded on a JEOL JNM-ECZ400S in CDCl3. HRMS was recorded on a Thermo scientific Q Exactive instrument. Mp were recorded on a Yanagimoto micro melting point apparatus. The 1H and 13C NMR data observed for 11,4, 33, 73, 83, 105, 222, 256, 266 were agreed with those previously reported in the literature. The 1H NMR data of 247 and 278 were in agreement with literature values.
26%	With magnesium In methanol at 60℃; for 6h;	1 Compound 14: 6 - [(E) -2- (4-tert-Butylphenyl) vinyl] -4-methoxy- 2 H-pyran-2-one (formula (14)) Metal Mg was heated in methanol (60 ° C.) and suspended. 4-methoxy-6-methyl-2-pyrone (0.20 g) and 4-tert-butylbenzaldehyde (0.41 ml, 1.6 mmol) were added thereto, and the mixture was heated at 60 ° C. for 6 hours. After cooling, it was acidified with acetic acid and extracted with ethyl acetate. The extract was concentrated under reduced pressure and then purified by reverse phase preparative HPLC (mobile phase: water-acetonitrile = 3: 7).Yield: 26%.

Reference： [1]Kumagai, Momochika; Nishikawa, Keisuke; Mishima, Takashi; Yoshida, Izumi; Ide, Masahiro; Koizumi, Keiko; Nakamura, Munetomo; Morimoto, Yoshiki [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 11, p. 2401 - 2406]
[2]Current Patent Assignee: JAPAN FOOD RES LAB - JP2018/123111, 2018, A Location in patent: Paragraph 0048

56
[ 672-89-9 ]
[ 2926-30-9 ]
4-methoxy-6-methyl-3-(trifluoromethyl)-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
5%	With tert.-butylhydroperoxide In dichloromethane; water at 20℃; for 18h;	4.4.16 4-Methoxy-6-methyl-3-(trifluoromethyl)-2H-pyran-2-one (21) A solution of pyrone 8 (0.17 g, 1.2 mmol) was prepared in 40 mL of DCM at room temperature, and NaSO2CF3 (0.51 g, 3.3 mmol) in 18 mL of water was added; then 70% aqueous tBuOOH (0.75 mL, 5.5 mmol) was added dropwise with vigorous stirring. After 18 h, the reaction solution was treated with NaHSO4(aq), and the product was extracted with DCM (3×30 mL). The organic layer was dried over Na2SO4, and after filtration, the solvent was evaporated. The product was further purified by silica gel column chromatography (EA/MeOH, 20:1) to afford small quantities of 21 as a white solid. Yield: 12 mg (5 %). 1H NMR (DMSO-d6) in ppm from TMS: δ 2.31 (s 3H), 4.01 (s 3H), 6.73 (s 1H). 19F NMR (DMSO-d6) in ppm from CFCl3: δ-55.88. IR in cm-1 (solid state): 1708, 1640, 1549, 1480, 1465, 1402, 1357, 1258, 1234, 1182, 1135, 1095, 1056, 1007, 954, 907, 821, 619, 496. HR-MS (CI-MS): Calcd. for [C8H7F3O3+H]+ 209.0426; found: 209.0430.

Reference： [1]Seo, Junhyeok; Sotman, Timothy E.; Sullivan, Eileen R.; Ellis, Bryan D.; Phung, Truc; Rose, Michael J. [Tetrahedron, 2017, vol. 73, # 31, p. 4519 - 4528]

57
[ 672-89-9 ]
[ 135-02-4 ]
(E)-4-methoxy-6-(2-methoxystyryl)-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	Stage #1: 4-methoxy-6-methyl-2H-pyran-2-one With potassium hexamethylsilazane In tetrahydrofuran at -78℃; for 0.166667h; Inert atmosphere; Stage #2: ortho-anisaldehyde In tetrahydrofuran at -78 - 0℃; for 0.666667h; Inert atmosphere; stereoselective reaction;	General Procedure for the synthesis of (E)-4-methoxy-6-styryl-2H-pyran-2-one using KHMDS General procedure: To a solution of Pyrone (1.0 mmol, 1.0 equiv.) in THF (10 mL) was added KHMDS (1M in THF, 1.6 mmol, 1.6 equiv.) at -78 °C under nitrogen and stirred for 10 min, and then aldehyde (1.6 mmol, 1.6 equiv.) in THF (5 mL) was added in dropwise and stirred at -78 °C for 10 min and then slowly warmed to 0 °C over 30 min under stirring. The reaction mixture was quenched with 10 % HCl solution, extracted with DCM, washed with brine, dried over Na2SO4, and concentrated to afford crude product was purified by silica gel (100-200 mesh) column chromatography, eluted with 30-40 % EtOAc in pet ether to afford the corresponding styryl pyrones.
57%	With magnesium methanolate Inert atmosphere; Reflux;	3.1.2 General procedure for the preparation of compounds 3-14 General procedure: Compound 2 (2.40mmol) and appropriate aldehydes (2.40mmol) in the presence of Mg(OCH3)2 (10mL) was refluxed under N2 overnight. After the reaction was completed as indicated by TLC, the mixture was concentrated under reduced pressure. The residue was purified with silica gel chromatography to obtain target compounds 3-14.
20%	With magnesium methanolate In methanol for 20h; Reflux; Inert atmosphere;	General Procedure for Preparation of Kavalactone Analogues 1-19. General procedure: Kavalactone analogues were prepared according to the previously reported method [24]. Amixture of 4-methoxy-6-methyl-pyran-2-one (25 mg, 0.178 mmol) and appropriate aldehyde (0.178mmol) in dimethoxymagnesium solution (60% in 2 mL methanol) was heated to reflux under anitrogen atmosphere for 20 h. After the reaction was completed, the mixture was concentrated underreduced pressure. The crude product was purified by flash column-chromatography (0%-40%EtOAc/cHexane) to give the title compound.

Reference： [1]Basu, Manas K.; Mukkanti, K.; Samala, Ramakrishna [Tetrahedron Letters, 2022, vol. 88]
[2]Li, Chanjuan; Cheng, Bao; Fang, Sai; Zhou, Huihao; Gu, Qiong; Xu, Jun [European Journal of Medicinal Chemistry, 2018, vol. 143, p. 114 - 122]
[3]Chang, Bill C. H.; Dilrukshi Herath, H. M. P.; Garcia-Bustos, José; Gasser, Robin B.; Hofmann, Andreas; Jabbar, Abdul; Ma, Guangxu; Nguyen, Nghi; Sleebs, Brad E.; Taki, Aya C.; Wang, Tao [Molecules, 2020, vol. 25, # 8]

58
[ 672-89-9 ]
[ 591-31-1 ]
(E)-4-methoxy-6-(3-methoxystyryl)-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%	With magnesium methanolate Inert atmosphere; Reflux;	3.1.2 General procedure for the preparation of compounds 3-14 General procedure: Compound 2 (2.40mmol) and appropriate aldehydes (2.40mmol) in the presence of Mg(OCH3)2 (10mL) was refluxed under N2 overnight. After the reaction was completed as indicated by TLC, the mixture was concentrated under reduced pressure. The residue was purified with silica gel chromatography to obtain target compounds 3-14.
18%	With magnesium methanolate In methanol for 20h; Reflux; Inert atmosphere;	General Procedure for Preparation of Kavalactone Analogues 1-19. General procedure: Kavalactone analogues were prepared according to the previously reported method [24]. Amixture of 4-methoxy-6-methyl-pyran-2-one (25 mg, 0.178 mmol) and appropriate aldehyde (0.178mmol) in dimethoxymagnesium solution (60% in 2 mL methanol) was heated to reflux under anitrogen atmosphere for 20 h. After the reaction was completed, the mixture was concentrated underreduced pressure. The crude product was purified by flash column-chromatography (0%-40%EtOAc/cHexane) to give the title compound.

Reference： [1]Li, Chanjuan; Cheng, Bao; Fang, Sai; Zhou, Huihao; Gu, Qiong; Xu, Jun [European Journal of Medicinal Chemistry, 2018, vol. 143, p. 114 - 122]
[2]Chang, Bill C. H.; Dilrukshi Herath, H. M. P.; Garcia-Bustos, José; Gasser, Robin B.; Hofmann, Andreas; Jabbar, Abdul; Ma, Guangxu; Nguyen, Nghi; Sleebs, Brad E.; Taki, Aya C.; Wang, Tao [Molecules, 2020, vol. 25, # 8]

59
[ 672-89-9 ]
[ 100-10-7 ]
[ 60427-78-3 ]

Yield	Reaction Conditions	Operation in experiment
32%	With magnesium methanolate Inert atmosphere; Reflux;	3.1.2 General procedure for the preparation of compounds 3-14 General procedure: Compound 2 (2.40mmol) and appropriate aldehydes (2.40mmol) in the presence of Mg(OCH3)2 (10mL) was refluxed under N2 overnight. After the reaction was completed as indicated by TLC, the mixture was concentrated under reduced pressure. The residue was purified with silica gel chromatography to obtain target compounds 3-14.
6%	With magnesium methanolate In methanol for 20h; Reflux; Inert atmosphere;	General Procedure for Preparation of Kavalactone Analogues 1-19. General procedure: Kavalactone analogues were prepared according to the previously reported method [24]. Amixture of 4-methoxy-6-methyl-pyran-2-one (25 mg, 0.178 mmol) and appropriate aldehyde (0.178mmol) in dimethoxymagnesium solution (60% in 2 mL methanol) was heated to reflux under anitrogen atmosphere for 20 h. After the reaction was completed, the mixture was concentrated underreduced pressure. The crude product was purified by flash column-chromatography (0%-40%EtOAc/cHexane) to give the title compound.

Reference： [1]Li, Chanjuan; Cheng, Bao; Fang, Sai; Zhou, Huihao; Gu, Qiong; Xu, Jun [European Journal of Medicinal Chemistry, 2018, vol. 143, p. 114 - 122]
[2]Chang, Bill C. H.; Dilrukshi Herath, H. M. P.; Garcia-Bustos, José; Gasser, Robin B.; Hofmann, Andreas; Jabbar, Abdul; Ma, Guangxu; Nguyen, Nghi; Sleebs, Brad E.; Taki, Aya C.; Wang, Tao [Molecules, 2020, vol. 25, # 8]

60
[ 14371-10-9 ]
[ 672-89-9 ]
4-methoxy-6-((1E,3E)-4-phenylbuta-1,3-dien-1-yl)-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	Stage #1: (E)-3-phenylpropenal With potassium hexamethylsilazane In tetrahydrofuran at -78℃; for 0.166667h; Inert atmosphere; Stage #2: 4-methoxy-6-methyl-2H-pyran-2-one In tetrahydrofuran at -78 - 0℃; for 1h; Inert atmosphere; stereoselective reaction;	General Procedure for the synthesis of (E)-4-methoxy-6-styryl-2H-pyran-2-one using KHMDS General procedure: To a solution of pyrone (1.0 mmol, 1.0 equiv.) in THF (10 mL) was added KHMDS (1M in THF, 1.6 mmol, 1.6 equiv.) at -78 °C under nitrogen and stirred for 10 min, and then aldehyde (1.6 mmol, 1.6 equiv.) in THF (5 mL) was added in dropwise and stirred at -78 °C for 10 min and then slowly warmed to 0 °C over 30 min under stirring. The reaction mixture was quenched with 10 % HCl solution, extracted with DCM, washed with brine, dried over Na2SO4, and concentrated to afford crude product was purified by silica gel (100-200 mesh) column chromatography, eluted with 30-40 % EtOAc in pet ether to afford the corresponding styryl pyrones.
43%	With magnesium methanolate Inert atmosphere; Reflux;	3.1.2 General procedure for the preparation of compounds 3-14 General procedure: Compound 2 (2.40mmol) and appropriate aldehydes (2.40mmol) in the presence of Mg(OCH3)2 (10mL) was refluxed under N2 overnight. After the reaction was completed as indicated by TLC, the mixture was concentrated under reduced pressure. The residue was purified with silica gel chromatography to obtain target compounds 3-14.

Reference： [1]Basu, Manas K.; Mukkanti, K.; Samala, Ramakrishna [Tetrahedron Letters, 2022, vol. 88]
[2]Li, Chanjuan; Cheng, Bao; Fang, Sai; Zhou, Huihao; Gu, Qiong; Xu, Jun [European Journal of Medicinal Chemistry, 2018, vol. 143, p. 114 - 122]

61
[ 98-01-1 ]
[ 672-89-9 ]
(E)-6-(2-(furan-2-yl)vinyl)-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	Stage #1: 4-methoxy-6-methyl-2H-pyran-2-one With potassium hexamethylsilazane In tetrahydrofuran at -78℃; for 0.166667h; Inert atmosphere; Stage #2: furfural In tetrahydrofuran at -78 - 0℃; for 0.666667h; Inert atmosphere; stereoselective reaction;	General Procedure for the synthesis of (E)-4-methoxy-6-styryl-2H-pyran-2-one using KHMDS General procedure: To a solution of Pyrone (1.0 mmol, 1.0 equiv.) in THF (10 mL) was added KHMDS (1M in THF, 1.6 mmol, 1.6 equiv.) at -78 °C under nitrogen and stirred for 10 min, and then aldehyde (1.6 mmol, 1.6 equiv.) in THF (5 mL) was added in dropwise and stirred at -78 °C for 10 min and then slowly warmed to 0 °C over 30 min under stirring. The reaction mixture was quenched with 10 % HCl solution, extracted with DCM, washed with brine, dried over Na2SO4, and concentrated to afford crude product was purified by silica gel (100-200 mesh) column chromatography, eluted with 30-40 % EtOAc in pet ether to afford the corresponding styryl pyrones.
41%	With magnesium methanolate Inert atmosphere; Reflux;	3.1.2 General procedure for the preparation of compounds 3-14 General procedure: Compound 2 (2.40mmol) and appropriate aldehydes (2.40mmol) in the presence of Mg(OCH3)2 (10mL) was refluxed under N2 overnight. After the reaction was completed as indicated by TLC, the mixture was concentrated under reduced pressure. The residue was purified with silica gel chromatography to obtain target compounds 3-14.

Reference： [1]Basu, Manas K.; Mukkanti, K.; Samala, Ramakrishna [Tetrahedron Letters, 2022, vol. 88]
[2]Li, Chanjuan; Cheng, Bao; Fang, Sai; Zhou, Huihao; Gu, Qiong; Xu, Jun [European Journal of Medicinal Chemistry, 2018, vol. 143, p. 114 - 122]

62
[ 672-89-9 ]
[ 446-52-6 ]
6-[(E)-2-(2-fluorophenyl)vinyl]-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With magnesium In methanol at 60℃; for 6h;	1 Compound 18: 6 - [(E) -2- (2-Fluorophenyl) vinyl] -4-methoxy- 2 H-pyran-2-one (formula (18)) Metal Mg was heated in methanol (60 ° C.) and suspended. 4-methoxy-6-methyl-2-pyrone (0.20 g) and 2-fluorobenzaldehyde (0.17 ml, 1.6 mmol) were added thereto, and the mixture was heated at 60 ° C. for 6 hours. After cooling, it was acidified with acetic acid and extracted with ethyl acetate. The extract was concentrated under reduced pressure and then purified by reverse phase preparative HPLC (mobile phase: water-acetonitrile = 3: 7).Yield: 71%.

Reference： [1]Current Patent Assignee: JAPAN FOOD RES LAB - JP2018/123111, 2018, A Location in patent: Paragraph 0053

63
[ 672-89-9 ]
[ 456-48-4 ]
6-[(E)-2-(3-fluorophenyl)vinyl]-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%	With magnesium In methanol at 60℃; for 6h;	1 Compound 19: 6 - [(E) -2- (3-Fluorophenyl) vinyl] -4-methoxy- 2 H-pyran-2-one (formula (19)) Metal Mg was heated in methanol (60 ° C.) and suspended. 4-methoxy-6-methyl-2-pyrone (0.20 g) and 3-fluorobenzaldehyde (0.17 ml, 1.6 mmol) were added thereto, and the mixture was heated at 60 ° C. for 6 hours. After cooling, it was acidified with acetic acid and extracted with ethyl acetate. The extract was concentrated under reduced pressure and then purified by reverse phase preparative HPLC (mobile phase: water-acetonitrile = 3: 7).Yield: 41%

Reference： [1]Current Patent Assignee: JAPAN FOOD RES LAB - JP2018/123111, 2018, A Location in patent: Paragraph 0054

64
[ 672-89-9 ]
[ 659-28-9 ]
(E)-4-methoxy-6-(4-(trifluoromethoxy)styryl)-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	Stage #1: 4-methoxy-6-methyl-2H-pyran-2-one With potassium hexamethylsilazane In tetrahydrofuran at -78℃; for 0.166667h; Inert atmosphere; Stage #2: p-trifluoromethoxybenzaldehyde In tetrahydrofuran at -78 - 0℃; for 0.666667h; Inert atmosphere; stereoselective reaction;	General Procedure for the synthesis of (E)-4-methoxy-6-styryl-2H-pyran-2-one using KHMDS General procedure: To a solution of Pyrone (1.0 mmol, 1.0 equiv.) in THF (10 mL) was added KHMDS (1M in THF, 1.6 mmol, 1.6 equiv.) at -78 °C under nitrogen and stirred for 10 min, and then aldehyde (1.6 mmol, 1.6 equiv.) in THF (5 mL) was added in dropwise and stirred at -78 °C for 10 min and then slowly warmed to 0 °C over 30 min under stirring. The reaction mixture was quenched with 10 % HCl solution, extracted with DCM, washed with brine, dried over Na2SO4, and concentrated to afford crude product was purified by silica gel (100-200 mesh) column chromatography, eluted with 30-40 % EtOAc in pet ether to afford the corresponding styryl pyrones.
15%	With magnesium methanolate In methanol for 20h; Reflux; Inert atmosphere;	General Procedure for Preparation of Kavalactone Analogues 1-19. General procedure: Kavalactone analogues were prepared according to the previously reported method [24]. Amixture of 4-methoxy-6-methyl-pyran-2-one (25 mg, 0.178 mmol) and appropriate aldehyde (0.178mmol) in dimethoxymagnesium solution (60% in 2 mL methanol) was heated to reflux under anitrogen atmosphere for 20 h. After the reaction was completed, the mixture was concentrated underreduced pressure. The crude product was purified by flash column-chromatography (0%-40%EtOAc/cHexane) to give the title compound.

Reference： [1]Basu, Manas K.; Mukkanti, K.; Samala, Ramakrishna [Tetrahedron Letters, 2022, vol. 88]
[2]Chang, Bill C. H.; Dilrukshi Herath, H. M. P.; Garcia-Bustos, José; Gasser, Robin B.; Hofmann, Andreas; Jabbar, Abdul; Ma, Guangxu; Nguyen, Nghi; Sleebs, Brad E.; Taki, Aya C.; Wang, Tao [Molecules, 2020, vol. 25, # 8]

65
[ 672-89-9 ]
[ 73960-07-3 ]
(E)-6-(4-(difluoromethoxy)styryl)-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
14%	With magnesium methanolate In methanol for 20h; Reflux; Inert atmosphere;	General Procedure for Preparation of Kavalactone Analogues 1-19. General procedure: Kavalactone analogues were prepared according to the previously reported method [24]. Amixture of 4-methoxy-6-methyl-pyran-2-one (25 mg, 0.178 mmol) and appropriate aldehyde (0.178mmol) in dimethoxymagnesium solution (60% in 2 mL methanol) was heated to reflux under anitrogen atmosphere for 20 h. After the reaction was completed, the mixture was concentrated underreduced pressure. The crude product was purified by flash column-chromatography (0%-40%EtOAc/cHexane) to give the title compound.

Reference： [1]Chang, Bill C. H.; Dilrukshi Herath, H. M. P.; Garcia-Bustos, José; Gasser, Robin B.; Hofmann, Andreas; Jabbar, Abdul; Ma, Guangxu; Nguyen, Nghi; Sleebs, Brad E.; Taki, Aya C.; Wang, Tao [Molecules, 2020, vol. 25, # 8]

66
[ 672-89-9 ]
[ 67-36-7 ]
(E)-4-methoxy-6-(4-phenoxystyryl)-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
22%	With magnesium methanolate In methanol for 20h; Reflux; Inert atmosphere;	General Procedure for Preparation of Kavalactone Analogues 1-19. General procedure: Kavalactone analogues were prepared according to the previously reported method [24]. Amixture of 4-methoxy-6-methyl-pyran-2-one (25 mg, 0.178 mmol) and appropriate aldehyde (0.178mmol) in dimethoxymagnesium solution (60% in 2 mL methanol) was heated to reflux under anitrogen atmosphere for 20 h. After the reaction was completed, the mixture was concentrated underreduced pressure. The crude product was purified by flash column-chromatography (0%-40%EtOAc/cHexane) to give the title compound.

Reference： [1]Chang, Bill C. H.; Dilrukshi Herath, H. M. P.; Garcia-Bustos, José; Gasser, Robin B.; Hofmann, Andreas; Jabbar, Abdul; Ma, Guangxu; Nguyen, Nghi; Sleebs, Brad E.; Taki, Aya C.; Wang, Tao [Molecules, 2020, vol. 25, # 8]

67
[ 672-89-9 ]
[ 1204-86-0 ]
(E)-4-methoxy-6-(4-morpholinostyryl)-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
7%	With magnesium methanolate In methanol for 20h; Reflux; Inert atmosphere;	General Procedure for Preparation of Kavalactone Analogues 1-19. General procedure: Kavalactone analogues were prepared according to the previously reported method [24]. Amixture of 4-methoxy-6-methyl-pyran-2-one (25 mg, 0.178 mmol) and appropriate aldehyde (0.178mmol) in dimethoxymagnesium solution (60% in 2 mL methanol) was heated to reflux under anitrogen atmosphere for 20 h. After the reaction was completed, the mixture was concentrated underreduced pressure. The crude product was purified by flash column-chromatography (0%-40%EtOAc/cHexane) to give the title compound.

Reference： [1]Chang, Bill C. H.; Dilrukshi Herath, H. M. P.; Garcia-Bustos, José; Gasser, Robin B.; Hofmann, Andreas; Jabbar, Abdul; Ma, Guangxu; Nguyen, Nghi; Sleebs, Brad E.; Taki, Aya C.; Wang, Tao [Molecules, 2020, vol. 25, # 8]

68
[ 27913-98-0 ]
[ 672-89-9 ]
(E)-4-methoxy-6-(4-(piperazin-1-yl)styryl)-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20%	With magnesium methanolate In methanol for 20h; Reflux; Inert atmosphere;	General Procedure for Preparation of Kavalactone Analogues 1-19. General procedure: Kavalactone analogues were prepared according to the previously reported method [24]. Amixture of 4-methoxy-6-methyl-pyran-2-one (25 mg, 0.178 mmol) and appropriate aldehyde (0.178mmol) in dimethoxymagnesium solution (60% in 2 mL methanol) was heated to reflux under anitrogen atmosphere for 20 h. After the reaction was completed, the mixture was concentrated underreduced pressure. The crude product was purified by flash column-chromatography (0%-40%EtOAc/cHexane) to give the title compound.

Reference： [1]Chang, Bill C. H.; Dilrukshi Herath, H. M. P.; Garcia-Bustos, José; Gasser, Robin B.; Hofmann, Andreas; Jabbar, Abdul; Ma, Guangxu; Nguyen, Nghi; Sleebs, Brad E.; Taki, Aya C.; Wang, Tao [Molecules, 2020, vol. 25, # 8]

69
[ 672-89-9 ]
[ 1571-08-0 ]
(E)-methyl 4-(2-(4-methoxy-2-oxo-2H-pyran-6-yl)vinyl)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
9%	With magnesium methanolate In methanol for 20h; Reflux; Inert atmosphere;	General Procedure for Preparation of Kavalactone Analogues 1-19. General procedure: Kavalactone analogues were prepared according to the previously reported method [24]. Amixture of 4-methoxy-6-methyl-pyran-2-one (25 mg, 0.178 mmol) and appropriate aldehyde (0.178mmol) in dimethoxymagnesium solution (60% in 2 mL methanol) was heated to reflux under anitrogen atmosphere for 20 h. After the reaction was completed, the mixture was concentrated underreduced pressure. The crude product was purified by flash column-chromatography (0%-40%EtOAc/cHexane) to give the title compound.

Reference： [1]Chang, Bill C. H.; Dilrukshi Herath, H. M. P.; Garcia-Bustos, José; Gasser, Robin B.; Hofmann, Andreas; Jabbar, Abdul; Ma, Guangxu; Nguyen, Nghi; Sleebs, Brad E.; Taki, Aya C.; Wang, Tao [Molecules, 2020, vol. 25, # 8]

70
[ 672-89-9 ]
[ 105-07-7 ]
(E)-4-(2-(4-methoxy-2-oxo-2H-pyran-6-yl)vinyl)benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
15%	With magnesium methanolate In methanol for 20h; Reflux; Inert atmosphere;	General Procedure for Preparation of Kavalactone Analogues 1-19. General procedure: Kavalactone analogues were prepared according to the previously reported method [24]. Amixture of 4-methoxy-6-methyl-pyran-2-one (25 mg, 0.178 mmol) and appropriate aldehyde (0.178mmol) in dimethoxymagnesium solution (60% in 2 mL methanol) was heated to reflux under anitrogen atmosphere for 20 h. After the reaction was completed, the mixture was concentrated underreduced pressure. The crude product was purified by flash column-chromatography (0%-40%EtOAc/cHexane) to give the title compound.

Reference： [1]Chang, Bill C. H.; Dilrukshi Herath, H. M. P.; Garcia-Bustos, José; Gasser, Robin B.; Hofmann, Andreas; Jabbar, Abdul; Ma, Guangxu; Nguyen, Nghi; Sleebs, Brad E.; Taki, Aya C.; Wang, Tao [Molecules, 2020, vol. 25, # 8]

71
[ 672-89-9 ]
[ 24964-64-5 ]
(E)-3-(2-(4-methoxy-2-oxo-2H-pyran-6-yl)vinyl)benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
10%	With magnesium methanolate In methanol for 20h; Reflux; Inert atmosphere;	General Procedure for Preparation of Kavalactone Analogues 1-19. General procedure: Kavalactone analogues were prepared according to the previously reported method [24]. Amixture of 4-methoxy-6-methyl-pyran-2-one (25 mg, 0.178 mmol) and appropriate aldehyde (0.178mmol) in dimethoxymagnesium solution (60% in 2 mL methanol) was heated to reflux under anitrogen atmosphere for 20 h. After the reaction was completed, the mixture was concentrated underreduced pressure. The crude product was purified by flash column-chromatography (0%-40%EtOAc/cHexane) to give the title compound.

Reference： [1]Chang, Bill C. H.; Dilrukshi Herath, H. M. P.; Garcia-Bustos, José; Gasser, Robin B.; Hofmann, Andreas; Jabbar, Abdul; Ma, Guangxu; Nguyen, Nghi; Sleebs, Brad E.; Taki, Aya C.; Wang, Tao [Molecules, 2020, vol. 25, # 8]

72
[ 672-89-9 ]
[ 52178-50-4 ]
(E)-methyl 3-(2-(4-methoxy-2-oxo-2H-pyran-6-yl)vinyl)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
8%	With magnesium methanolate In methanol for 20h; Reflux; Inert atmosphere;	General Procedure for Preparation of Kavalactone Analogues 1-19. General procedure: Kavalactone analogues were prepared according to the previously reported method [24]. Amixture of 4-methoxy-6-methyl-pyran-2-one (25 mg, 0.178 mmol) and appropriate aldehyde (0.178mmol) in dimethoxymagnesium solution (60% in 2 mL methanol) was heated to reflux under anitrogen atmosphere for 20 h. After the reaction was completed, the mixture was concentrated underreduced pressure. The crude product was purified by flash column-chromatography (0%-40%EtOAc/cHexane) to give the title compound.

Reference： [1]Chang, Bill C. H.; Dilrukshi Herath, H. M. P.; Garcia-Bustos, José; Gasser, Robin B.; Hofmann, Andreas; Jabbar, Abdul; Ma, Guangxu; Nguyen, Nghi; Sleebs, Brad E.; Taki, Aya C.; Wang, Tao [Molecules, 2020, vol. 25, # 8]

73
[ 672-89-9 ]
[ 65873-72-5 ]
(E)-4-methoxy-6-(2-(6-methoxypyridin-3-yl)vinyl)-2H-pyran-2-on [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
10%	With magnesium methanolate In methanol for 20h; Reflux; Inert atmosphere;	General Procedure for Preparation of Kavalactone Analogues 1-19. General procedure: Kavalactone analogues were prepared according to the previously reported method [24]. Amixture of 4-methoxy-6-methyl-pyran-2-one (25 mg, 0.178 mmol) and appropriate aldehyde (0.178mmol) in dimethoxymagnesium solution (60% in 2 mL methanol) was heated to reflux under anitrogen atmosphere for 20 h. After the reaction was completed, the mixture was concentrated underreduced pressure. The crude product was purified by flash column-chromatography (0%-40%EtOAc/cHexane) to give the title compound.

Reference： [1]Chang, Bill C. H.; Dilrukshi Herath, H. M. P.; Garcia-Bustos, José; Gasser, Robin B.; Hofmann, Andreas; Jabbar, Abdul; Ma, Guangxu; Nguyen, Nghi; Sleebs, Brad E.; Taki, Aya C.; Wang, Tao [Molecules, 2020, vol. 25, # 8]

74
[ 672-89-9 ]
[ 54774-80-0 ]

Yield	Reaction Conditions	Operation in experiment
94%	With sulfuric acid; nitric acid at 0 - 20℃; Inert atmosphere;

Reference： [1]Beaudry, Christopher M.; Points, Gary L.; Stout, Kenneth T. [Chemistry - A European Journal, 2020, vol. 26, # 70, p. 16655 - 16658]

75
[ 672-89-9 ]
[ 678995-12-5 ]
C₂₄H₃₄O₅Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With magnesium In methanol at 65℃; for 5h; Further stages;	(E)-6-(4-Hydroxystyryl)-4-methoxy-2H-piran-2-ones. General procedure: Magnesium (9 mmol, 216 mg) was dissolved inanhydrous methanol (7 mL). To the resulting solutionwas added dropwise a solution of the correspondingbenzaldehyde (3 mmol) and 4-methoxy-6-methyl-2H-pyran-2-one (504 mg, 3.6 mmol) in methanol(5 mL). The reaction mixture was boiled for 5 h, thencooled to room temperature and concentrated on arotary evaporator. The residue was dissolved in tetrahydrofuran(25 mg) and tetrabutylammonium fluoride(940 mg, 3.6 mmol) and acetic acid (1 drop) wereadded. The resulting mixture was stirred at room temperaturefor 12 h. Then the reaction mixture was evaporated,the residue was dissolved in chloroform (10 mL),washed with saturated sodium chloride solution (30 mL),dried over anhydrous Na2SO4 and evaporated. Theresulting product was purified using column chromatography(eluent: chloroform-methanol, 50 : 1).

Reference： [1]Sokolov; Myasnyanko; Baleeva; Baranov [Russian Journal of Bioorganic Chemistry, 2021, vol. 47, # 1, p. 334 - 337][Bioorg. Khim., 2021, vol. 47, # 1, p. 173 - 176,4]

76
[ 672-89-9 ]
2,5-dimethoxy-4-((triisopropylsilyl)oxy)benzaldehyde [ No CAS ]
C₂₅H₃₆O₆Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With magnesium In methanol at 65℃; for 5h; Further stages;	(E)-6-(4-Hydroxystyryl)-4-methoxy-2H-piran-2-ones. General procedure: Magnesium (9 mmol, 216 mg) was dissolved inanhydrous methanol (7 mL). To the resulting solutionwas added dropwise a solution of the correspondingbenzaldehyde (3 mmol) and 4-methoxy-6-methyl-2H-pyran-2-one (504 mg, 3.6 mmol) in methanol(5 mL). The reaction mixture was boiled for 5 h, thencooled to room temperature and concentrated on arotary evaporator. The residue was dissolved in tetrahydrofuran(25 mg) and tetrabutylammonium fluoride(940 mg, 3.6 mmol) and acetic acid (1 drop) wereadded. The resulting mixture was stirred at room temperaturefor 12 h. Then the reaction mixture was evaporated,the residue was dissolved in chloroform (10 mL),washed with saturated sodium chloride solution (30 mL),dried over anhydrous Na2SO4 and evaporated. Theresulting product was purified using column chromatography(eluent: chloroform-methanol, 50 : 1).

Reference： [1]Sokolov; Myasnyanko; Baleeva; Baranov [Russian Journal of Bioorganic Chemistry, 2021, vol. 47, # 1, p. 334 - 337][Bioorg. Khim., 2021, vol. 47, # 1, p. 173 - 176,4]

77
[ 672-89-9 ]
(2R,3R)-3-[(tert-butyldimethylsilyl)oxy]-5,5-bis(ethylthio)-2-[(2′-methoxyethoxy)-methoxy]-pentanal [ No CAS ]
6-{(2′S,3′S,4′R)-4′-[(tert-butyldimethylsilyl)oxy]-6′,6′-bis(ethylthio)-2′-hydroxy-3′-[(2′′-methoxyethoxy)methoxy]hexyl}-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	Stage #1: 4-methoxy-6-methyl-2H-pyran-2-one With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 2h; Stage #2: (2R,3R)-3-[(tert-butyldimethylsilyl)oxy]-5,5-bis(ethylthio)-2-[(2′-methoxyethoxy)-methoxy]-pentanal In tetrahydrofuran at -78℃; for 3h; diastereoselective reaction;

Reference： [1]Bach, Thorsten; Koser, Lilla; Lechner, Vivian Miles [Angewandte Chemie - International Edition, 2021, vol. 60, # 37, p. 20269 - 20273][Angew. Chem., 2021, vol. 133, # 37, p. 20431 - 20435]

78
[ 672-89-9 ]
[ 1122-91-4 ]
(E)-6-(4-bromostyryl)-4-methoxy-2H-pyran-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	Stage #1: 4-methoxy-6-methyl-2H-pyran-2-one With potassium hexamethylsilazane In tetrahydrofuran at -78℃; for 0.166667h; Inert atmosphere; Stage #2: 4-bromo-benzaldehyde In tetrahydrofuran at -78 - 0℃; for 0.666667h; Inert atmosphere; stereoselective reaction;	General Procedure for the synthesis of (E)-4-methoxy-6-styryl-2H-pyran-2-one using KHMDS General procedure: To a solution of Pyrone (1.0 mmol, 1.0 equiv.) in THF (10 mL) was added KHMDS (1M in THF, 1.6 mmol, 1.6 equiv.) at -78 °C under nitrogen and stirred for 10 min, and then aldehyde (1.6 mmol, 1.6 equiv.) in THF (5 mL) was added in dropwise and stirred at -78 °C for 10 min and then slowly warmed to 0 °C over 30 min under stirring. The reaction mixture was quenched with 10 % HCl solution, extracted with DCM, washed with brine, dried over Na2SO4, and concentrated to afford crude product was purified by silica gel (100-200 mesh) column chromatography, eluted with 30-40 % EtOAc in pet ether to afford the corresponding styryl pyrones.