Name: 520-18-3|3,5,7-Trihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one|98%
Brand: Ambeed
SKU: A272671
Rating: 98 (32 reviews)

1
[ 520-18-3 ]
[ 77-78-1 ]
[ 15486-34-7 ]

Yield	Reaction Conditions	Operation in experiment
70%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetone at 20℃; for 1h;	Semi-synthesis of flavones 8-10 from kaempferol Flavones 8-10 were obtained as previously reported [29]. Compound 8 was obtained by methylation of kaempferol (100 mg) (Sigma-Aldrich, France), using 4 equiv. of dimethyl sulfate (Me2SO4) and 2equiv. of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The reaction wasperformed at room temperature in dried acetone for 1 h. After precipitation and washing with iced water, obtained residues were solubilized with ethyl acetate (15 mL) and treated with a solution of 1 NHCl (3 mL). Finally, reaction product was extracted with ethyl acetate(3 x 10 mL) and the organic phase was washed with a saturated solution of NaCl, then dried over Na2SO4. Paper filtration and solvent evaporation provided a mixture, which was purified by silica gel column chromatography using as eluent dichloromethane/methanol (95/5, v/v, yield: 70%). For preparation of compounds 9 and 10, kaempferol (80mg, 0.28mmol) was acetylated using acetic anhydride in dry pyridine. The reaction was performed by stirring for 15min at room temperature. After precipitation and washing with iced water, recrystallization in CH2Cl2/CH3OH (9/1, v/v) provided 108mg (0.26mmol) of triacetyl derivative 9 (yield: 95%). The same procedure for the semi-synthesis of 9 was applied for 4h instead of 15min. After precipitation and washing with iced water, recrystallization in CH2Cl2/CH3OH (9/1, v/v) provided 120mg (0.26mmol) of tetra acetyl derivative 10 (yield: 95%). 1H and 13C NMR data of 8-10 were in accordance with those previously reported [29,30].
	With potassium hydroxide
	With potassium carbonate; acetone

Reference： [1]Beaugeard, Laureen; Beserra de Alencar Filho, Edilson; Guedes da Silva Almeida, Jackson Roberto; Michel, Sylvie; Picot, Laurent; Gonçalves de Oliveira-Júnior, Raimundo; Grougnet, Raphaël; Marcoult-Fréville, Nolwenn; Prunier, Grégoire; Quintans-Júnior, Lucindo José; Simões Mourão, Eduard David [Chemico-Biological Interactions, 2020, vol. 325]
[2]Kondo et al. [Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1929, vol. 49, p. 232,236; dtsch. Ref. S. 35][Chem.Abstr., 1929, p. 3230]
[3]Rao; Seshadri [Proceedings - Indian Academy of Sciences, Section A, 1947, # 25, p. 444,445]

2
[ 520-18-3 ]
[ 108-24-7 ]
[ 16274-11-6 ]

Yield	Reaction Conditions	Operation in experiment
95%	With pyridine at 20℃; for 4h;	Semi-synthesis of flavones 8-10 from kaempferol General procedure: Flavones 8-10 were obtained as previously reported [29]. Compound 8 was obtained by methylation of kaempferol (100 mg) (Sigma-Aldrich, France), using 4 equiv. of dimethyl sulfate (Me2SO4) and 2equiv. of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The reaction wasperformed at room temperature in dried acetone for 1 h. After precipitation and washing with iced water, obtained residues were solubilized with ethyl acetate (15 mL) and treated with a solution of 1 NHCl (3 mL). Finally, reaction product was extracted with ethyl acetate(3 x 10 mL) and the organic phase was washed with a saturated solution of NaCl, then dried over Na2SO4. Paper filtration and solvent evaporation provided a mixture, which was purified by silica gel column chromatography using as eluent dichloromethane/methanol (95/5, v/v, yield: 70%). For preparation of compounds 9 and 10, kaempferol (80mg, 0.28mmol) was acetylated using acetic anhydride in dry pyridine. The reaction was performed by stirring for 15min at room temperature. After precipitation and washing with iced water, recrystallization in CH2Cl2/CH3OH (9/1, v/v) provided 108mg (0.26mmol) of triacetyl derivative 9 (yield: 95%). The same procedure for the semi-synthesis of 9 was applied for 4h instead of 15min. After precipitation and washing with iced water, recrystallization in CH2Cl2/CH3OH (9/1, v/v) provided 120mg (0.26mmol) of tetra acetyl derivative 10 (yield: 95%). 1H and 13C NMR data of 8-10 were in accordance with those previously reported [29,30].
94%	With pyridine at 20℃;	3,4′,5,7-Tetra-O-acetylkaempferol(1) Aceticanhydride(60 mL)was added to the solution of dry kaempferol (4 g, 13.99 mmol)in pyridine(30 mL), and the mixture was allowed to standovernight at ambienttemperature. After complete conversionmonitored by TLC, the solvent was removedand the residue was poured into crushed ice with vigorous stirring. Theabundant resulting off-white precipitate was recovered by filtration and washedwith cold water and then methanol, and dried in air.The crude product wascrystallized from acetone/95% ethanol (1:3) to afford 1 (5.95 g, 94%) ascolorless needles, mp:183-184C. IR (cm-1): 1775, 1661, 1631, 1503, 1476, 1435, 1370,1186, 1158, 1122,1081, 1013.1H NMR (600 MHz, CDCl3): δ = 7.84 (d, J= 8.7 Hz, 2H), 7.32 (d, J= 2.1Hz, 1H), 7.26 (d, J= 8.7 Hz, 2H), 6.87 (d, J= 2.1 Hz, 1H), 2.43(s, 3H), 2.34 (s, 6H), 2.32 (s, 3H). 13CNMR (150 MHz, CDCl3): δ = 170.24, 169.39, 168.99,167.98, 167.91, 157.10, 154.91, 154.38, 153.08, 150.61, 134.08, 129.76, 127.16,122.21, 114.97, 113.97, 109.10, 21.30,21.18, 20.71. ESI-HRMS: 477.0807 [M+Na]+(calcd. for C23H18O10Na: 477.0792).
94%	With pyridine

90%	With pyridine at 20℃;
65%	With pyridine at 15℃; for 12h; Inert atmosphere;	169 Example 169: [4-(3,5,7-triacetoxy-4-oxo-chromen-2-yl)phenyl] acetate To a mixture of 3,5,7-trihydroxy-2-(4-hydroxyphenyl)chromen-4-one (2 g) in pyridine (15 mL) was added acetyl acetate (30 g), and then the mixture was stirred at 15 °C for 12 hr under N2 atmosphere.The solvent was removed under reduced pressure and the residue was poured into crushed ice with vigorous stirring. The solid precipidate was collected by filtration and washed with cold water and then with methanol. The desired compound [4-(3,5,7-triacetoxy-4-oxo-chromen-2-yl)phenyl] acetate (2.1 g, 65% yield) was obtained as a white solid. LCMS: 455.0 (M÷H÷) 1H NMR (400 MHz, CDCI3): O 7.858 (d, 2H), 7.339 (d, 1H), 7.278 7.257 (m, 2H), 6.883 (d, 1H), 2.447 (s, 3H), 2.357 (s, 6H), 2.333 (s, 3H) ppm
65%	With pyridine at 15℃; for 12h; Inert atmosphere;	1 Compound 8: [4-(3,5,7-triacetoxy-4-oxo-chromen-2-yl)phenyl] acetate To a mixture of 3,5,7-trihydroxy-2-(4-hydroxyphenyl)chromen-4-one (2 g) in pyridine (15 ml_) was added acetyl acetate (30 g), and then the mixture was stirred at 15 °C for 12 hr under N2 atmosphere. The solvent was removed under reduced pressure and the residue was poured into crushed ice with vigorous stirring. The solid precipitate was collected by filtration and washed with cold water and then with methanol. Compound 8 (2.1 g, 65% yield) was obtained as a white solid. LCMS: 455.0 (M+H+) 1 H NMR (400 MHz, CDCI3) 7.858 (d, 2H), 7.339 (d, 1 H), 7.278 7.257 (m, 2H), 6.883 (d, 1 H), 2.447 (s, 3H), 2.357 (s, 6H), 2.333 (s, 3H)
65%	With pyridine at 15℃; for 12h; Inert atmosphere;	1 Compound 20: [4-(3,5,7-triacetoxy-4-oxo-chromen-2-yl)phenyl] acetate To a mixture of 3,5,7-trihydroxy-2-(4-hydroxyphenyl)chromen-4-one (2 g) in pyridine (15 mL) was added acetyl acetate (30 g), and then the mixture was stirred at 15 °C for 12 hr under N atmosphere. The solvent was removed under reduced pressure and the residue was poured into crushed ice with vigorous stirring. The solid precipitate was collected by filtration and washed with cold water and then with methanol. Compound 20 (2.1 g,65% yield) was obtained as a white solid. LCMS: 455.0 (M+H+) 1 H (0797) NMR (400 MHz, CDCIs) d 7.858 (d, 2H), 7.339 (d,1 H), 7.278 7.257 (m, 2H),6.883 (d,1 H), 2.447 (s,3H), 2.357 (s,6H), 2.333 (s,3H)
65%	With pyridine at 15℃; for 12h; Inert atmosphere;	Compound 8: [4-(3,5,7-triacetoxy-4-oxo-chromen-2-yl)phenyl]acetate To a mixture of 3,5,7-trihydroxy-2-(4-hydroxyphenyl)chromen-4-one (2 g) in pyridine (15 ml_) was added acetyl acetate (30 g), and then the mixture was stirred at 15 C for 12 hr under N2 atmosphere. The solvent was removed under reduced pressure and the residue was poured into crushed ice with vigorous stirring. The solid precipidate was collected by filtration and washed with cold water and then with methanol. Compound 8 (2.1 g, 65% yield) was obtained as a white solid. LCMS: 455.0 (M+H+) 1H NMR (400 MHz, CDC ) 7.858 (d, 2H), 7.339 (d, 1H), 7.278 7.257 (m, 2H), 6.883 (d, 1H), 2.447 (S,3H), 2.357 (s, 6H), 2.333 (S,3H)
	With pyridine
15 mg	With dmap In pyridine Ambient temperature;
	With pyridine at 20℃;
15 mg	With pyridine; dmap at 20℃;
	With pyridine at 20℃;
	With triethylamine In dichloromethane for 1h;

Reference： [1]Beaugeard, Laureen; Beserra de Alencar Filho, Edilson; Guedes da Silva Almeida, Jackson Roberto; Michel, Sylvie; Picot, Laurent; Gonçalves de Oliveira-Júnior, Raimundo; Grougnet, Raphaël; Marcoult-Fréville, Nolwenn; Prunier, Grégoire; Quintans-Júnior, Lucindo José; Simões Mourão, Eduard David [Chemico-Biological Interactions, 2020, vol. 325]
[2]Mei, Qinggang; Wang, Chun; Yuan, Weicheng; Zhang, Guolin [Beilstein Journal of Organic Chemistry, 2015, vol. 11, p. 288 - 293]
[3]Mei, Qinggang; Wang, Chun; Zhao, Zhigang; Yuan, Weicheng; Zhang, Guolin [Beilstein Journal of Organic Chemistry, 2015, vol. 11, p. 1220 - 1225]
[4]Zheng, Yuanyuan; Pu, Wenchen; Li, Jiao; Shen, Xianyan; Zhou, Qiang; Fan, Xin; Yang, Sheng-Yong; Yu, Yamei; Chen, Qiang; Wang, Chun; Wu, Xin; Peng, Yong [Chemistry - An Asian Journal, 2019, vol. 14, # 1, p. 130 - 134]
[5]Current Patent Assignee: FLAGSHIP PIONEERING INC - WO2018/226732, 2018, A1 Location in patent: Page/Page column 152
[6]Current Patent Assignee: FLAGSHIP PIONEERING INC - WO2019/236765, 2019, A1 Location in patent: Page/Page column 44
[7]Current Patent Assignee: FLAGSHIP PIONEERING INC - WO2019/236775, 2019, A1 Location in patent: Page/Page column 67; 75
[8]Current Patent Assignee: FLAGSHIP PIONEERING INC - WO2019/236772, 2019, A1 Location in patent: Page/Page column 57; 135-136
[9]Chawla, H. Mohindra; Johny, C. J.; Mittal, Ram S. [Bulletin de la Societe Chimique de France, 1989, # 1, p. 82 - 87]
[10]Prawat, Hunsa; Mahidol, Chulabhorn; Ruchirawat, Somsak; Prawat, Uma; Tuntiwachwuttikul, Pittaya; et al. [Phytochemistry, 1995, vol. 40, # 4, p. 1167 - 1174]
[11]Diaz, Jesus G.; Carmona, Armando J.; Torres, Fernando; Quintana, Jose; Estevez, Francisco; Herz, Werner [Planta Medica, 2008, vol. 74, # 2, p. 171 - 174]
[12]Location in patent: experimental part Anam, Edet M. [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2009, vol. 48, # 3, p. 423 - 429]
[13]Location in patent: experimental part Marin, Clotilde; Boutaleb-Charki, Samira; Diaz, Jesus G.; Huertas, Oscar; Rosales, Maria J.; Perez-Cordon, Gregorio; Guitierrez-Sanchez, Ramon; Sanchez-Moreno, Manuel [Journal of Natural Products, 2009, vol. 72, # 6, p. 1069 - 1074]
[14]Cheng, Mao-Sheng; Fan, Zhan-Fang; Fu, Ya; Ho, Sai-Tim; Hu, Chun; Liu, Yang; Shaw, Pang-Chui; Wang, Jian; Wen, Rui; Zhang, Lei [Molecules, 2019, vol. 24, # 17]

3
[ 520-18-3 ]
[ 77-78-1 ]
[ 16692-52-7 ]

Yield	Reaction Conditions	Operation in experiment
90%	With potassium carbonate In acetone at 50℃; for 48h;	1.1 1. Preparation of compound a1 Accurately weigh kaempferol (20.00mmol, 6.00g) and dissolve it in 5mL acetone, add K2CO3 (160.00mmol, 23.20g), stir at 50°C and add dimethyl sulfate (100.00mmol, 9.94mL) dropwise.After 48h, TLC monitors the reaction progress. After the reaction is over, add an appropriate amount of dilute sodium hydroxide solution to quench the reaction, and adjust the pH to neutral with dilute hydrochloric acid.Concentrate the reaction solution, add distilled water and shake well, extract 3 times with ethyl acetate, dry with anhydrous sodium sulfate, filter and concentrate to obtain a crude product. The crude product was separated and purified by gel column chromatography to obtain a1 (6.12 g, yield 90.0%) as a yellow solid.
90%	With potassium carbonate In acetone at 50℃;
86.3%	With potassium carbonate In acetone at 50℃; for 48h;	1 Example 1: Preparation method of Compound 1 Weighing naphthol (0.7mmol, 200mg)And anhydrous potassium carbonate (5 mmol, 691.05 mg) in a reaction flask, adding 9 mL of acetone,Stir at 50 ° C and add dimethyl sulfate (5 mmol, 379 μL).TLC was monitored (DCM: MeOH = 30:1). After 48h treatment.The reaction was quenched by adding an appropriate amount of dilute sodium hydroxide solution (removing the toxic dimethyl sulfate), and the pH was adjusted to neutral with dilute hydrochloric acid.The reaction mixture was concentrated, washed with EtOAc EtOAc EtOAc.The crude product was purified by gel column chromatography to yield yellow solid. The yield was 86.3%.

	With potassium carbonate
	With potassium carbonate In acetone for 4h; Heating;
	With potassium hydroxide In water; acetone

Reference： [1]Current Patent Assignee: JIANGSU UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN112110902, 2020, A Location in patent: Paragraph 0037-0045
[2]Attaribo, Thomas; Gui, Zhongzheng; Huang, Gaiqun; Jin, Byung Rae; Lee, Kwang Sik; Tang, Liumei; Xin, Xiangdong; Zeng, Qinglei; Zhang, Ning; Zhang, Ran; Zhang, Yueyue [Journal of Natural Products, 2021, vol. 84, # 5, p. 1534 - 1543]
[3]Current Patent Assignee: TIANJIN MEDICAL UNIVERSITY - CN109988138, 2019, A Location in patent: Paragraph 0012-0013
[4]Joseph-Nathan, P.; Abramo-Bruno, D.; Torres, Ma. A. [Phytochemistry, 1981, vol. 20, p. 313 - 318]
[5]Ji, Xiao-duo; Melman, Neli; Jacobson, Kenneth A. [Journal of Medicinal Chemistry, 1996, vol. 39, # 3, p. 781 - 788]
[6]Chen, Hongping; Ding, Haiyan; Hu, Yuan; Li, Dan; Liu, Youping; You, Qiang [Journal of Agricultural and Food Chemistry, 2021, vol. 69, # 43, p. 12705 - 12716]

4
[ 520-18-3 ]
[ 1592-70-7 ]
[ 491-54-3 ]

Reference： [1]Phytochemistry,1980,vol. 19,p. 741 - 746

5
[ 569-92-6 ]
[ 520-18-3 ]

Reference： [1]Chemistry of Natural Compounds,1981,vol. 17,p. 225 - 230
Khimiya Prirodnykh Soedinenii,1981,vol. 17,p. 298 - 303

6
[ 520-18-3 ]
[ 7697-37-2 ]
[ 51-28-5 ]
[ 616-82-0 ]
[ 144-62-7 ]

Reference： [1]Archiv der Pharmazie,1909,vol. 247,p. 452,453

7
[ 480-41-1 ]
[ 520-36-5 ]
[ 520-18-3 ]
[ 118333-31-6 ]
(2R,3S)-dihydrokaempferol [ No CAS ]

Reference： [1]Phytochemistry,2002,vol. 60,p. 589 - 593

8
[ 480-41-1 ]
[ 520-36-5 ]
[ 520-18-3 ]
[ 118333-31-6 ]
(2R,3S)-dihydrokaempferol [ No CAS ]

Reference： [1]Phytochemistry,2002,vol. 60,p. 589 - 593

9
[ 480-41-1 ]
cis-dihydrokaempferol [ No CAS ]
trans-dihydrokaempferol [ No CAS ]
[ 520-18-3 ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 3117 - 3126

10
[ 480-41-1 ]
cis-dihydrokaempferol [ No CAS ]
trans-dihydrokaempferol [ No CAS ]
[ 520-36-5 ]
[ 520-18-3 ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 3117 - 3126

11
[ 19895-95-5 ]
[ 520-18-3 ]

Reference： [1]Chemistry of Natural Compounds,2006,vol. 42,p. 736 - 737

12
[ 5128-44-9 ]
[ 520-18-3 ]

Reference： [1]Journal of the Chinese Chemical Society,2001,vol. 48,p. 201 - 206

13
kaempferol 3-O-galactoside [ No CAS ]
[ 59-23-4 ]
[ 520-18-3 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; water for 0.75h; Reflux;
	With hydrogenchloride In water at 100℃; for 0.5h;	Sugar and aglycone analysis General procedure: Acid hydrolysis of flavonoids was carried out in 2M HCl, at 100°C for 30min. After cooling, HCl was removed by evaporation and the hydolysate was dried under a stream of N2. Aglycones formed by acid hydrolysis were analyzed by LC-MS as described above using commercially available standards. Sugars released by hydrolysis were analyzed by a glucose assay kit and a galactose assay kit according to the manufactures procedures to determine their absolute configuration.

Reference： [1]Location in patent: experimental part Liu, ChangDa; Chen, Jing; Wang, JinHui [Chemistry of Natural Compounds, 2009, vol. 45, # 6, p. 808 - 810]
[2]Hirayama, Chikara; Ono, Hiroshi; Meng, Yan; Shimada, Toru; Daimon, Takaaki [Phytochemistry, 2013, vol. 94, p. 108 - 112]

14
[ 520-18-3 ]
[ 18162-48-6 ]
[ 1246814-11-8 ]

Yield	Reaction Conditions	Operation in experiment
90%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 20℃; for 0.25h;
81%	In N,N-dimethyl-formamide at 20℃; Inert atmosphere;	1.2 Step 2: Preparation of 3,7,4'-tri-O- t-butyldimethylsilyl kaempferol Under nitrogen, the kaempferol (2g, 7mmol) and TBSCl (4.2g, 28mmol) was dissolvedDry DMF (5mL), and room temperature, TLC track to complete the reaction. The reaction systemExtracted with DCM, washed with water, then washed with a saturated brine, dried over anhydrous sodium sulfate.The resulting filtrate was concentrated under reduced pressure column chromatography to obtain the objective product (3.6g, 81%);

Reference： [1]Location in patent: experimental part Yang, Weizhun; Sun, Jiansong; Lu, Wenxiang; Li, Yan; Shan, Lei; Han, Wei; Zhang, Wei-Dong; Yu, Biao [Journal of Organic Chemistry, 2010, vol. 75, # 20, p. 6879 - 6888]
[2]Current Patent Assignee: JIANGXI NORMAL UNIVERSITY - CN105273028, 2016, A Location in patent: Paragraph 0042; 0043

15
[ 23405-70-1 ]
[ 520-18-3 ]

Yield	Reaction Conditions	Operation in experiment
72%	With palladium 10% on activated carbon; hydrogen In tetrahydrofuran; methanol for 12h;
58%	With hydrogen; palladium(II) hydroxide In tetrahydrofuran; methanol at 20℃; for 3h;

Reference： [1]Kim, Sugyeom; Lannigan, Deborah A.; Li, Yu; Lin, Lin; O'Doherty, George A.; Sayasith, Peyton R.; Tarr, Ariel T.; Wright, Eric B.; Yasmin, Sharia [Journal of Organic Chemistry, 2020, vol. 85, # 6, p. 4279 - 4288]
[2]Yamasaki, Kazuaki; Hishiki, Ryogo; Kato, Eisuke; Kawabata, Jun [ACS Medicinal Chemistry Letters, 2011, vol. 2, # 1, p. 17 - 21]

16
[ 724434-08-6 ]
[ 520-18-3 ]

Yield	Reaction Conditions	Operation in experiment
60%	With potassium metabisulphite In ethanol at 100℃;	(d) Flavonols 6, 6a, 6b, 6c and 6d General procedure: Dihydroflavonols (5, 0.3 mmol) in ethanol (2.5 ml) was added to potassium metabisulphite, (5.0 ml, 20%) and heated at 100 °C (5-8 h). The reaction mixture is poured into crushed ice. The centrifuged product was purified by column (SiO2) chromatography. The purity of final products were analyzed by HPLC and NMR (Supplementary data).
23.4 g	With oxygen; potassium carbonate In ethanol for 8h; Reflux;	4.3 3) Preparation of kaempferol oxide 36.3 g of crude dihydrokaempferol obtained in step 2.3) was put into a reaction bottle.Add 185ml of 70% ethanol,Stir well,Add 6.8 g of anhydrous potassium carbonate,Passing oxygen,Then heated to reflux,Oxidation reaction,High performance liquid chromatography,The kaempferol is no longer increased as the end point of the reaction control.The reaction was completed after about 8 hours.Drop to room temperature and leave overnight.filter,Obtained a yellow solid,Add 180g of water,Filtered after 2 hours of reflux,The filter cake is washed and dried,Obtained 23.4g of kaempferol,The content is 98% (HPLC).
	With FLAVONOL SYNTHASE Enzymatic reaction;

Reference： [1]Location in patent: experimental part Pandurangan; Bose, Chinchu; Banerji [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 18, p. 5328 - 5330]
[2]Current Patent Assignee: SHAANXI JIAHE PHYTOCHEM - CN109369593, 2019, A Location in patent: Paragraph 0041-0042; 0051-0052; 0061-0062; 0063; 0071-0072
[3]Current Patent Assignee: OTSUKA HOLDINGS CO LTD - WO2022/45091, 2022, A1 Location in patent: Paragraph 0092

17
C₁₀H₉BrO₂ [ No CAS ]
[ 520-18-3 ]
[ 1338577-12-0 ]

Yield	Reaction Conditions	Operation in experiment
18.5%	Stage #1: kaempferol With potassium carbonate In 1,4-dioxane for 1.5h; Reflux; Stage #2: C₁₀H₉BrO₂ In 1,4-dioxane Reflux; Stage #3: With hydrogenchloride In water	7.2. General procedure for the synthesis of compounds 3 General procedure: To a mixture of kaempferol (1.2 eq) and K2CO3 (1.2 eq) in 1,4-dioxane (10 ml), which was stirred for 90 min while maintaining gentle reflux, was added a solution of the 2 compounds (1 eq) in 1,4-dioxane (5 ml) for 30 min. The reaction mixture was refluxed until the starting material disappeared, as indicated by TLC (CH2Cl2:MeOH, 95:5). The solvent was removed from the reaction mixture under reduced pressure. Water was added, the aqueous phase was neutralized (to pH 7) with 1 M HCl, and then extracted with ethyl acetate. The organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated. The crude product was purified using a gel-permeation chromatograph (HW-40; CH2Cl2:MeOH, 1:1) and prepared-TLC to give a yellow solid product.
	Stage #1: kaempferol With potassium carbonate In 1,4-dioxane for 1.5h; Reflux; Stage #2: C₁₀H₉BrO₂ In 1,4-dioxane Reflux;	3.1 Example 3 General Procedure for the Synthesis of Compounds General procedure: To a mixture of kaempferol (1.2 eq) and K2CO3 (1.2 eq) in 1,4-dioxane (10 ml), which was stirred for 90 minutes while maintaining gentle reflux, was added a solution of the compound III (1 eq) in 1,4-dioxane (2 nil) for 30 minutes. The reaction mixture was refluxed until the starting material disappeared, as indicated by TLC. The solvent was removed from the reaction mixture under reduced pressure. Water was added, the aqueous phase was neutralized (to pH 7) with 1 M HCl, and then extracted with ethyl acetate. The organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated. The crude product was purified using a gel-permeation chromatograph (HW-40; CH2Cl2-MeOH, 1:1) and preparation-TLC to give compound series I as shown in Formula (6).

Reference： [1]Location in patent: experimental part Qin, Nan; Li, Chun-Bao; Jin, Mei-Na; Shi, Li-Huan; Duan, Hong-Quan; Niu, Wen-Yan [European Journal of Medicinal Chemistry, 2011, vol. 46, # 10, p. 5189 - 5195]
[2]Current Patent Assignee: TIANJIN MEDICAL UNIVERSITY - US2013/231492, 2013, A1 Location in patent: Paragraph 0030; 0031

18
[ 520-18-3 ]
[ 74-88-4 ]
[ 16692-52-7 ]

Yield	Reaction Conditions	Operation in experiment
78%	With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 15h; Inert atmosphere;	3,5,7-Trimethoxy-2-(4-methoxyphenyl)-4H-chromen-4-one General procedure: To a stirred solution of kaempferol (286 mg, 1.0mmol) in dry DMF (5 mL) was added K2CO3 (829 mg, 6.0mmol) and CH3I (851 mg, 6 mmol). After the addition, the mixture wasstirred for 15 h at room temperature. The reaction mixture was then dilutedwith CH2Cl2 (20 mL) and poured into aqueous HCl (0.1 M)(10 mL). The organic layer was separated, washed with H2O (3×10 mL)and dried over Mg2SO4. After concentrated to drynessunder reduced pressure, the crude product was purified by column chromatographyon silica (petroleum ether/ethyl acetate 1:1) to afford the known compound 247 (266 mg, 78%) as a white solid

Reference： [1]Lu, Kui; Chu, Jie; Wang, Haomeng; Fu, Xiaoli; Quan, Dewu; Ding, Hongxia; Yao, Qingwei; Yu, Peng [Tetrahedron Letters, 2013, vol. 54, # 47, p. 6345 - 6348]

19
[ 520-18-3 ]
[ 74-88-4 ]
[ 15486-34-7 ]

Yield	Reaction Conditions	Operation in experiment
55%	With sodium carbonate In N,N-dimethyl-formamide at 20℃; for 15h; Inert atmosphere;	5-Hydroxy-3,4',7-trimethoxyflavone (18) To a stirred solution of kaempferol (286 mg, 1.0mmol) in dry DMF (5 mL) was added Na2CO3 (477 mg, 4.5mmol) and CH3I (639 mg, 4.5 mmol). After the addition, the mixturewas stirred for 15 h at room temperature. The reaction mixture was then dilutedwith CH2Cl2 (20 mL) and poured into aqueous HCl (0.1 M)(10 mL). The organic layer was separated, washed with H2O (3×10 mL)and dried over Mg2SO4. After concentrated to drynessunder reduced pressure, the crude product was purified by column chromatographyon silica (petroleum ether/ethyl acetate 3:1) to afford the known compound 184 (181 mg, 55%) as a yellow solid.

Reference： [1]Lu, Kui; Chu, Jie; Wang, Haomeng; Fu, Xiaoli; Quan, Dewu; Ding, Hongxia; Yao, Qingwei; Yu, Peng [Tetrahedron Letters, 2013, vol. 54, # 47, p. 6345 - 6348]

20
[ 1454577-75-3 ]
[ 59-23-4 ]
[ 520-18-3 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride In water at 100℃; for 0.5h;	Sugar and aglycone analysis General procedure: Acid hydrolysis of flavonoids was carried out in 2M HCl, at 100°C for 30min. After cooling, HCl was removed by evaporation and the hydolysate was dried under a stream of N2. Aglycones formed by acid hydrolysis were analyzed by LC-MS as described above using commercially available standards. Sugars released by hydrolysis were analyzed by a glucose assay kit and a galactose assay kit according to the manufactures procedures to determine their absolute configuration.

Reference： [1]Hirayama, Chikara; Ono, Hiroshi; Meng, Yan; Shimada, Toru; Daimon, Takaaki [Phytochemistry, 2013, vol. 94, p. 108 - 112]

21
[ 520-18-3 ]
[ 491-54-3 ]

Reference： [1]Beilstein Journal of Organic Chemistry,2015,vol. 11,p. 288 - 293

22
[ 520-18-3 ]
[ 569-92-6 ]

Reference： [1]Beilstein Journal of Organic Chemistry,2015,vol. 11,p. 288 - 293

23
kaempferol 3-O-[(6-O-E-p-coumaroyl)-β-D-glucopyranosyl(1→2)]-α-L-rhamnopyranosyl(1→6)}-β-D-galactopyranoside-7-O-α-L-rhamnopyranoside [ No CAS ]
[ 520-18-3 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: kaempferol 3-O-[(6-O-E-p-coumaroyl)-β-D-glucopyranosyl(1→2)]-α-L-rhamnopyranosyl(1→6)}-β-D-galactopyranoside-7-O-α-L-rhamnopyranoside With sodium hydroxide; ascorbic acid at 20℃; for 2h; Darkness; Stage #2: With hydrogenchloride; water In methanol at 100℃; for 2h;	3.7. Alkaline and Acid Hydrolysis of Flavonoids The water phases were dried and then desalted by SPE (Oasis HLB 30 mg). Methanol SPE eluates,containing deacylated flavonoids, were dried and subjected to acid hydrolysis (1 mL of 2M HCl, 2 h,100 °C). Aglycones were then extracted with ethyl acetate (3 × 1 mL), dried with a stream of nitrogen,dissolved in 50% methanol, and identified by UPLC-ESI-MS. Chromatographic separations wereperformed on a ACQUITY BEH C18 (100 × 2.1 mm, 1.7 μm; Waters) column (40 °C). The mobile phases were water with 0.1% FA (A) and in acetonitrile with 0.1% FA (B). Samples were separated (400 μL·min-1) with the following gradient: 0-1 min, 15% B; 1-11 min, 15%-95% B; 11-13 min, 95%B; 13-13.1 min, 95%-15% B; 13.1-15 min, 15% B. Mass spectra were obtained in negative ionization mode, MS parameters were as follows: capillary voltage 2.8 kV; cone voltage 45 V; source temperature 140 °C, desolvation temperature 350 °C, cone gas flow (nitrogen) 100 L·h-1 desolvation gas flow 800 L·h-1.Sugar-containing aqueous layers were neutralized with Amberlite IRA-400 (OH- form) [33]. After drying, the samples were used to determine the absolute configuration of the constituent monosaccharides.

Reference： [1]Zuchowski, Jerzy; Pecio, Lukasz; Stochmal, Anna [Molecules, 2014, vol. 19, # 11, p. 18152 - 18178]

24
kaempferol 3-O-[(6-O-E-caffeoyl)-β-D-glucopyranosyl(1→2)]-β-D-galactopyranoside-7-O-(2-O-E-caffeoyl')-β-D-glucuropyranoside [ No CAS ]
[ 520-18-3 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: kaempferol 3-O-[(6-O-E-caffeoyl)-β-D-glucopyranosyl(1→2)]-β-D-galactopyranoside-7-O-(2-O-E-caffeoyl')-β-D-glucuropyranoside With sodium hydroxide; ascorbic acid at 20℃; for 2h; Darkness; Stage #2: With hydrogenchloride; water In methanol at 100℃; for 2h;	3.7. Alkaline and Acid Hydrolysis of Flavonoids The water phases were dried and then desalted by SPE (Oasis HLB 30 mg). Methanol SPE eluates,containing deacylated flavonoids, were dried and subjected to acid hydrolysis (1 mL of 2M HCl, 2 h,100 °C). Aglycones were then extracted with ethyl acetate (3 × 1 mL), dried with a stream of nitrogen,dissolved in 50% methanol, and identified by UPLC-ESI-MS. Chromatographic separations wereperformed on a ACQUITY BEH C18 (100 × 2.1 mm, 1.7 μm; Waters) column (40 °C). The mobile phases were water with 0.1% FA (A) and in acetonitrile with 0.1% FA (B). Samples were separated (400 μL·min-1) with the following gradient: 0-1 min, 15% B; 1-11 min, 15%-95% B; 11-13 min, 95%B; 13-13.1 min, 95%-15% B; 13.1-15 min, 15% B. Mass spectra were obtained in negative ionization mode, MS parameters were as follows: capillary voltage 2.8 kV; cone voltage 45 V; source temperature 140 °C, desolvation temperature 350 °C, cone gas flow (nitrogen) 100 L·h-1 desolvation gas flow 800 L·h-1.Sugar-containing aqueous layers were neutralized with Amberlite IRA-400 (OH- form) [33]. After drying, the samples were used to determine the absolute configuration of the constituent monosaccharides.

Reference： [1]Zuchowski, Jerzy; Pecio, Lukasz; Stochmal, Anna [Molecules, 2014, vol. 19, # 11, p. 18152 - 18178]

25
kaempferol 3-O-β-D-glucopyranosyl(1→2)-β-D-galactopyranoside-7-O-β-D-glucuropyranoside [ No CAS ]
[ 520-18-3 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: kaempferol 3-O-β-D-glucopyranosyl(1→2)-β-D-galactopyranoside-7-O-β-D-glucuropyranoside With sodium hydroxide; ascorbic acid at 20℃; for 2h; Darkness; Stage #2: With hydrogenchloride; water In methanol at 100℃; for 2h;	3.7. Alkaline and Acid Hydrolysis of Flavonoids The water phases were dried and then desalted by SPE (Oasis HLB 30 mg). Methanol SPE eluates,containing deacylated flavonoids, were dried and subjected to acid hydrolysis (1 mL of 2M HCl, 2 h,100 °C). Aglycones were then extracted with ethyl acetate (3 × 1 mL), dried with a stream of nitrogen,dissolved in 50% methanol, and identified by UPLC-ESI-MS. Chromatographic separations wereperformed on a ACQUITY BEH C18 (100 × 2.1 mm, 1.7 μm; Waters) column (40 °C). The mobile phases were water with 0.1% FA (A) and in acetonitrile with 0.1% FA (B). Samples were separated (400 μL·min-1) with the following gradient: 0-1 min, 15% B; 1-11 min, 15%-95% B; 11-13 min, 95%B; 13-13.1 min, 95%-15% B; 13.1-15 min, 15% B. Mass spectra were obtained in negative ionization mode, MS parameters were as follows: capillary voltage 2.8 kV; cone voltage 45 V; source temperature 140 °C, desolvation temperature 350 °C, cone gas flow (nitrogen) 100 L·h-1 desolvation gas flow 800 L·h-1.Sugar-containing aqueous layers were neutralized with Amberlite IRA-400 (OH- form) [33]. After drying, the samples were used to determine the absolute configuration of the constituent monosaccharides.

Reference： [1]Zuchowski, Jerzy; Pecio, Lukasz; Stochmal, Anna [Molecules, 2014, vol. 19, # 11, p. 18152 - 18178]

26
kaempferol 3-O-[(6-O-E-caffeoyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-7-O-β-D-glucuropyranoside [ No CAS ]
[ 520-18-3 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: kaempferol 3-O-[(6-O-E-caffeoyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-7-O-β-D-glucuropyranoside With sodium hydroxide; ascorbic acid at 20℃; for 2h; Darkness; Stage #2: With hydrogenchloride; water In methanol at 100℃; for 2h;	3.7. Alkaline and Acid Hydrolysis of Flavonoids The water phases were dried and then desalted by SPE (Oasis HLB 30 mg). Methanol SPE eluates,containing deacylated flavonoids, were dried and subjected to acid hydrolysis (1 mL of 2M HCl, 2 h,100 °C). Aglycones were then extracted with ethyl acetate (3 × 1 mL), dried with a stream of nitrogen,dissolved in 50% methanol, and identified by UPLC-ESI-MS. Chromatographic separations wereperformed on a ACQUITY BEH C18 (100 × 2.1 mm, 1.7 μm; Waters) column (40 °C). The mobile phases were water with 0.1% FA (A) and in acetonitrile with 0.1% FA (B). Samples were separated (400 μL·min-1) with the following gradient: 0-1 min, 15% B; 1-11 min, 15%-95% B; 11-13 min, 95%B; 13-13.1 min, 95%-15% B; 13.1-15 min, 15% B. Mass spectra were obtained in negative ionization mode, MS parameters were as follows: capillary voltage 2.8 kV; cone voltage 45 V; source temperature 140 °C, desolvation temperature 350 °C, cone gas flow (nitrogen) 100 L·h-1 desolvation gas flow 800 L·h-1.Sugar-containing aqueous layers were neutralized with Amberlite IRA-400 (OH- form) [33]. After drying, the samples were used to determine the absolute configuration of the constituent monosaccharides.

Reference： [1]Zuchowski, Jerzy; Pecio, Lukasz; Stochmal, Anna [Molecules, 2014, vol. 19, # 11, p. 18152 - 18178]

27
kaempferol 3-O-[(6-O-E-p-coumaroyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-7-O-β-D-glucuropyranoside [ No CAS ]
[ 520-18-3 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: kaempferol 3-O-[(6-O-E-p-coumaroyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-7-O-β-D-glucuropyranoside With sodium hydroxide; ascorbic acid at 20℃; for 2h; Darkness; Stage #2: With hydrogenchloride; water In methanol at 100℃; for 2h;	3.7. Alkaline and Acid Hydrolysis of Flavonoids The water phases were dried and then desalted by SPE (Oasis HLB 30 mg). Methanol SPE eluates,containing deacylated flavonoids, were dried and subjected to acid hydrolysis (1 mL of 2M HCl, 2 h,100 °C). Aglycones were then extracted with ethyl acetate (3 × 1 mL), dried with a stream of nitrogen,dissolved in 50% methanol, and identified by UPLC-ESI-MS. Chromatographic separations wereperformed on a ACQUITY BEH C18 (100 × 2.1 mm, 1.7 μm; Waters) column (40 °C). The mobile phases were water with 0.1% FA (A) and in acetonitrile with 0.1% FA (B). Samples were separated (400 μL·min-1) with the following gradient: 0-1 min, 15% B; 1-11 min, 15%-95% B; 11-13 min, 95%B; 13-13.1 min, 95%-15% B; 13.1-15 min, 15% B. Mass spectra were obtained in negative ionization mode, MS parameters were as follows: capillary voltage 2.8 kV; cone voltage 45 V; source temperature 140 °C, desolvation temperature 350 °C, cone gas flow (nitrogen) 100 L·h-1 desolvation gas flow 800 L·h-1.Sugar-containing aqueous layers were neutralized with Amberlite IRA-400 (OH- form) [33]. After drying, the samples were used to determine the absolute configuration of the constituent monosaccharides.

Reference： [1]Zuchowski, Jerzy; Pecio, Lukasz; Stochmal, Anna [Molecules, 2014, vol. 19, # 11, p. 18152 - 18178]

28
kaempferol 3-O-[(6-O-E-feruloyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-7-O-β-D-glucuropyranoside [ No CAS ]
[ 520-18-3 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: kaempferol 3-O-[(6-O-E-feruloyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-7-O-β-D-glucuropyranoside With sodium hydroxide; ascorbic acid at 20℃; for 2h; Darkness; Stage #2: With hydrogenchloride; water In methanol at 100℃; for 2h;	3.7. Alkaline and Acid Hydrolysis of Flavonoids The water phases were dried and then desalted by SPE (Oasis HLB 30 mg). Methanol SPE eluates,containing deacylated flavonoids, were dried and subjected to acid hydrolysis (1 mL of 2M HCl, 2 h,100 °C). Aglycones were then extracted with ethyl acetate (3 × 1 mL), dried with a stream of nitrogen,dissolved in 50% methanol, and identified by UPLC-ESI-MS. Chromatographic separations wereperformed on a ACQUITY BEH C18 (100 × 2.1 mm, 1.7 μm; Waters) column (40 °C). The mobile phases were water with 0.1% FA (A) and in acetonitrile with 0.1% FA (B). Samples were separated (400 μL·min-1) with the following gradient: 0-1 min, 15% B; 1-11 min, 15%-95% B; 11-13 min, 95%B; 13-13.1 min, 95%-15% B; 13.1-15 min, 15% B. Mass spectra were obtained in negative ionization mode, MS parameters were as follows: capillary voltage 2.8 kV; cone voltage 45 V; source temperature 140 °C, desolvation temperature 350 °C, cone gas flow (nitrogen) 100 L·h-1 desolvation gas flow 800 L·h-1.Sugar-containing aqueous layers were neutralized with Amberlite IRA-400 (OH- form) [33]. After drying, the samples were used to determine the absolute configuration of the constituent monosaccharides.

Reference： [1]Zuchowski, Jerzy; Pecio, Lukasz; Stochmal, Anna [Molecules, 2014, vol. 19, # 11, p. 18152 - 18178]

29
[ 133-89-1 ]
[ 520-18-3 ]
[ 16290-07-6 ]

Yield	Reaction Conditions	Operation in experiment
80%	With glycosyltransferase from Carthamus tinctorius (L_.) (Honghua) recombinant In dimethyl sulfoxide at 30℃; for 12h; Enzymatic reaction;
	With flavonoid 7-O-glucosyltransferase from Andrographis paniculata In methanol at 30℃; for 12h; Enzymatic reaction;	3.5. Enzyme assay and product identification General procedure: All assays and incubations were performed in 100 ll of 50mM Tris-HCl (pH 8.0)containing 8 lg of purified proteins, 200 lM aglycone, and 3200 lM UDP-glucose.The reactions were incubated at 30 C for 12 h and terminated by the addition of200 ll of methanol. The products of the reactions were filtered through a 0.22-lmnylon syringe filter and analyzed using a Waters Acquity UPLC-I-Class system(Waters Corp., Milford, MA) with an Acquity UPLC BEH C18 column (1.7 mm,2.1mm 50 mm). The column temperature was set to 40 C, and the flow rate was400 lL/min. Mobile phase A was a 0.1% formic acid aqueous solution, and mobilephase B was acetonitrile. Gradient programs were used to analyze the reaction mixtures(Table 1). The total conversion rate was calculated to be one percent of the sumof the peak areas of the substrate and product(s). The experiment was performed inthe ESI (-) mode as previously described [17].

Reference： [1]Xie, Kebo; Ridao, Chen; Li, Jianhua; Wang, Ruishan; Chen, Dawei; Dou, Xiaoxiang; Dai, Jungui [Organic Letters, 2014, vol. 16, # 18, p. 4874 - 4877]
[2]Li, Yuan; Gao, Wei; Huang, Lu-Qi [Journal of Asian Natural Products Research, 2020, vol. 22, # 3, p. 279 - 286]

30
[ 520-18-3 ]
[ 118525-40-9 ]

Reference： [1]Beilstein Journal of Organic Chemistry,2015,vol. 11,p. 1220 - 1225
[2]Chemistry - An Asian Journal,2019,vol. 14,p. 130 - 134

31
[ 520-18-3 ]
[ 489-32-7 ]

Reference： [1]Beilstein Journal of Organic Chemistry,2015,vol. 11,p. 1220 - 1225

32
[ 520-18-3 ]
[ 142-61-0 ]
3,7,4'-tri(O-hexanoyl)kaempferol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With triethylamine In acetone at 0 - 20℃; for 3h;
61%	With triethylamine In acetone at 20℃; Inert atmosphere;	3.2 Step 2:3,7,4'- tri -O- hexanoyl kaempferolPreparation Under nitrogen, the kaempferol (2.3g, 8mmol) and hexanoyl chloride (3.7ml, 26.4mmol) was dissolved in dry acetone (100mL), and then added triethylamine (3.65ml, 26.4mmol). Reaction at room temperature, TLC track to complete the reaction. After the reaction system was concentrated under reduced pressure column chromatography to obtain the objective product (2.8g, 61%).

Reference： [1]Liao, Jin-Xi; Fan, Nai-Li; Liu, Hui; Tu, Yuan-Hong; Sun, Jian-Song [Organic and Biomolecular Chemistry, 2016, vol. 14, # 4, p. 1221 - 1225]
[2]Current Patent Assignee: JIANGXI NORMAL UNIVERSITY - CN105273028, 2016, A Location in patent: Paragraph 0063; 0064; 0065

33
[ 520-18-3 ]
[ 100-39-0 ]
3,4',7-tri-O-benzylkaempferol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With potassium carbonate In acetone
72%	With potassium carbonate In N,N-dimethyl-formamide at 20℃; Inert atmosphere;	2.2 Step 2:3,7,4'- three -O- benzyl kaempferolPreparation Under nitrogen, the kaempferol (4.2g, 15mmol) and benzyl bromide (5.7ml, 48mmol) was dissolved in dry DMF (20mL), and then potassium carbonate powder (7.3g, 53mmol). Reaction at room temperature, TLC track to complete the reaction. The reaction system was extracted with DCM, washed with water, then washed with a saturated brine, dried over anhydrous sodium sulfate. The resulting filtrate was concentrated under reduced pressure column chromatography to obtain the objective product (6g, 72%).

Reference： [1]Liao, Jin-Xi; Fan, Nai-Li; Liu, Hui; Tu, Yuan-Hong; Sun, Jian-Song [Organic and Biomolecular Chemistry, 2016, vol. 14, # 4, p. 1221 - 1225]
[2]Current Patent Assignee: JIANGXI NORMAL UNIVERSITY - CN105273028, 2016, A Location in patent: Paragraph 0053; 0054; 0055

34
kaempferol 3-O-β-D-glucopyranosyl-(1→2)-α-L-rhamnopyranosyl-(1→2)-O-β-D-glucopyranosyl-7-O-β-D-glucopyranoside [ No CAS ]
[ 520-18-3 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride In methanol; water at 80℃; for 2h;	Acid hydrolysis of compound 2 Three mg of compound 2 was hydrolyzed with 10% HCl (3.5 ml) in aqueous methanol at 80°C for 2 hour, after the removal of the solvent the reaction mixture was diluted by distilled water,whereby it give aglycone and sugar, the aglycone was identified via CO-PC with authentic sample and sugar moieties were detected via CO-TLC with authentic sugar markers in system(CHCl3:Me2CO:MeOH:H2O, 3:3:3:1 and CH2Cl2:MeOH:H2O, 6:9:1) respectively.

Reference： [1]Hamed, Manal M.; El-Amin, Samir M.; Refahy, Laila A.; Soliman, El-Sayed A.; Mansour, Wafaa A.; Abu Taleb, Hoda M.; Morsi, Eman A. [Oriental Journal of Chemistry, 2015, vol. 31, # 3, p. 1621 - 1634]

35
[ 41290-68-0 ]
[ 520-18-3 ]
RuCl(kaempferol)(DMSO)<SUB>3</SUB> [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	Stage #1: kaempferol With triethylamine In methanol Stage #2: tetrakis(dimethylsulfoxide)dichlororuthenium(II) In methanol at 20℃; for 10h; Darkness;	Synthesis of Complex 1. A kaem methanolic solution was prepared by dissolving kaem (286 mg, 1.00 mmol) into methanol (25 mL) with an equimolar quantity of triethylamine(139 μL, 1.00 mmol). Next, RuCl2(DMSO)4 (484 mg,1.00 mmol) was also dissolved in methanol (25 mL) in aseparate flask. The RuCl2(DMSO)4 solution was then addeddropwise into the prepared kaem solution. The reaction mixture was stirred for 10 h at room temperature; Al foilwas used to protect the reaction mixture from light. Thecolor of the reaction mixture changed from light yellow toreddish brown (Scheme 2). The solvent was removed byrotary evaporation to afford the crude product (~650 mg).Purification of Complex 1. The crude product was dissolvedin methylene chloride (MC) and loaded onto asilica-packed column. The column was eluted using a 10%methanol/MC solution, and the product was monitored bythin-layer chromatography (TLC). The solvent of the collectedproduct was removed by rotary evaporation followedby drying in a vacuum oven at 80C. The purified samplewas recrystallized from a minimum amount of methanol, ina 4 mL vial. The vial was wrapped with Al foil, with severalholes punctured on the top, to protect the product fromlight. The container was stored in a vibration-free location,at room temperature for 24 h. Dark brown block-shapedmicrocrystals were collected (282 mg, yield: 43%). Elementalanalysis data for RuC22H39ClO14S3 [RuC21H27-ClO9S3 4H2O CH3OH]: Calcd. (%) for RuC22H39ClO14S3: C 34.74, H 5.31, S 12.65; found: C 34.69, H5.06, S 12.76. 1H NMR (methanol-d4) δ (ppm): 8.402 (d,J = 8.50 Hz, 2H, Ar-H), 6.915 (d, J = 8.50 Hz, 2H, Ar-H),6.385 (s, 1H, 8-CH), 6.179 (s, 1H, 6-CH), 2.676 (s,18H, CH3).

Reference： [1]Shao, Mingwei; Gang, Jongback; Kim, Sanghyo; Yoon, Minyoung [Bulletin of the Korean Chemical Society, 2016, vol. 37, # 10, p. 1625 - 1631]

36
[ 520-18-3 ]
[ 108-24-7 ]
[ 35688-42-7 ]

Yield	Reaction Conditions	Operation in experiment
95%	With pyridine at 20℃; for 4h; Inert atmosphere;	4.2.4 Semi-synthesis of flavone 16 80mg (0.28mmol) of commercial kaempferol (11) were acetylated by stirring with acetic anhydride in anhydrous pyridine at room temperature for 4h. The crudes were precipitated and washed in ice water. The resulting was recrystallized in CH2Cl2/ CH3OH (9/1, v/v) to furnish 120mg (0.26mmol) of tetraacetyl derivative 16 (yield: 95%).

Reference： [1]Mai, Linh H.; Chabot, Guy G.; Grellier, Philippe; Quentin, Lionel; Dumontet, Vincent; Poulain, Cyril; Espindola, Laila S.; Michel, Sylvie; Vo, Hue T.B.; Deguin, Brigitte; Grougnet, Raphaël [European Journal of Medicinal Chemistry, 2015, vol. 93, p. 93 - 100]

37
[ 520-18-3 ]
[ 108-24-7 ]
[ 143724-69-0 ]

Yield	Reaction Conditions	Operation in experiment
95%	With pyridine at 20℃; for 0.25h; Inert atmosphere;	4.2.3 Semi-synthesis of flavone 15 80mg (0.28mmol) of commercial kaempferol (11) were acetylated by stirring with acetic anhydride in dry pyridine at room temperature for 15min. The crudes were precipitated and washed in iced water. The resulting was recrystallized in CH2Cl2/ CH3OH (9/1, v/v) to furnish 108mg (0.26mmol) of triacetyl derivative 15 (yield: 95%).
95%	With pyridine at 20℃; for 0.25h;	Semi-synthesis of flavones 8-10 from kaempferol General procedure: Flavones 8-10 were obtained as previously reported [29]. Compound 8 was obtained by methylation of kaempferol (100 mg) (Sigma-Aldrich, France), using 4 equiv. of dimethyl sulfate (Me2SO4) and 2equiv. of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The reaction wasperformed at room temperature in dried acetone for 1 h. After precipitation and washing with iced water, obtained residues were solubilized with ethyl acetate (15 mL) and treated with a solution of 1 NHCl (3 mL). Finally, reaction product was extracted with ethyl acetate(3 x 10 mL) and the organic phase was washed with a saturated solution of NaCl, then dried over Na2SO4. Paper filtration and solvent evaporation provided a mixture, which was purified by silica gel column chromatography using as eluent dichloromethane/methanol (95/5, v/v, yield: 70%). For preparation of compounds 9 and 10, kaempferol (80mg, 0.28mmol) was acetylated using acetic anhydride in dry pyridine. The reaction was performed by stirring for 15min at room temperature. After precipitation and washing with iced water, recrystallization in CH2Cl2/CH3OH (9/1, v/v) provided 108mg (0.26mmol) of triacetyl derivative 9 (yield: 95%). The same procedure for the semi-synthesis of 9 was applied for 4h instead of 15min. After precipitation and washing with iced water, recrystallization in CH2Cl2/CH3OH (9/1, v/v) provided 120mg (0.26mmol) of tetra acetyl derivative 10 (yield: 95%). 1H and 13C NMR data of 8-10 were in accordance with those previously reported [29,30].
90.5%	With pyridine at 100 - 140℃;	2.1 Example 2: Preparation of 6-prenyl substituted apigenin 1) 2 g of apigenin, 3 to 4 equivalents of acetic anhydride, 1 to 2 times of pyridine,The reaction is carried out at 100 to 140 ° C for 2 to 24 hours, the product is IIIa, and the yield is 90.5%.

Reference： [1]Mai, Linh H.; Chabot, Guy G.; Grellier, Philippe; Quentin, Lionel; Dumontet, Vincent; Poulain, Cyril; Espindola, Laila S.; Michel, Sylvie; Vo, Hue T.B.; Deguin, Brigitte; Grougnet, Raphaël [European Journal of Medicinal Chemistry, 2015, vol. 93, p. 93 - 100]
[2]Beaugeard, Laureen; Beserra de Alencar Filho, Edilson; Guedes da Silva Almeida, Jackson Roberto; Michel, Sylvie; Picot, Laurent; Gonçalves de Oliveira-Júnior, Raimundo; Grougnet, Raphaël; Marcoult-Fréville, Nolwenn; Prunier, Grégoire; Quintans-Júnior, Lucindo José; Simões Mourão, Eduard David [Chemico-Biological Interactions, 2020, vol. 325]
[3]Current Patent Assignee: GUANGDONG JINJUNKANG BIO TECH - CN109369748, 2019, A Location in patent: Paragraph 0031; 0032

38
[ 553-26-4 ]
[ 520-18-3 ]
2C₁₅H₁₀O₆*C₁₀H₈N₂*2H₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With water In ethanol; acetone at 25℃; for 3h;	KAE·BPY··2H2O Kaempferol (14.3 mg, 0.05 mmol) and 4,40-bipyridine dehydrate (4.8 mg, 0.025 mmol) were combined in8.0 mL ethanol and 2.0 mL acetone with stirring at 25 C for 3 h. The filtrate was evaporated slowly at room temperature; block yellow crystals were obtained after 5 days (Fig. S1a). The resulting products were characterized by single crystal X-ray diffraction, XPRD, IR and NMR. The other two cocrystals were prepared under similar conditions and post-processing except for the molar ration of flavonols and 4,40-bipyridine dehydrate. IR data (KBr cm1): 3693w,3211s, 2974s, 2687 m, 2642 m, 2614 m,1988w,1898w,1761w,1611s,1525 m, 1454 m, 1375 m, 1320 m, 1180s, 1081s, 1017s, 835s, 733w,634 m, 576 m, 477s, 436 m (Fig. S2) [32].

Reference： [1]Zhang, Yu-Nan; Yin, He-Mei; Zhang, Yu; Zhang, Da-Jun; Su, Xin; Kuang, Hai-Xue [Journal of Molecular Structure, 2017, vol. 1130, p. 199 - 207]

39
kaempferol-7-O-α-L-rhamnoside [ No CAS ]
[ 73-34-7 ]
[ 520-18-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid
	With hydrogenchloride In methanol at 80℃; for 4h;	3.6. Acid Hydrolysis of Compounds 4-8 General procedure: 5 mg of each compound was separately refluxed with 2M HCl in MeOH (5 mL) at80 C for 4 h in a water bath. The reaction mixture was evaporated, and the hydrolysateafter dilution with H2O (10 mL) was extracted with CHCl3 (3 10 mL). The CHCl3 extractswere evaporated to afford the aglycones, which were identified as kampferol for 4 and 7,isorhamnetin for 5, quercetin for 6 and benzyl alcohol for 8 by comparison with authenticsamples, respectively. The aqueous layer was neutralized with sodium carbonate andconcentrated to 1 mL under reduced pressure. The residue was compared with standardsugars by Si gel TLC [(CHCl3-MeOH-H2O:30:12:4), 9 mL of lower layer and 1 mL ofHOAc], which indicated the sugars to be L-rhamnose in compounds 4, 6 and 7 and glucosein compounds 5 and 8.

Reference： [1]Alaniya; Sutiashvili; Kavtaradze, N. Sh.; Skhirtladze [Chemistry of Natural Compounds, 2017, vol. 53, # 6, p. 1202 - 1203][Khim. Prir. Soedin., 2017, # 6, p. 1018 - 1019,2]
[2]Mohammed, Hamdoon A.; Abd El-Wahab, Mohammed F.; Shaheen, Usama; Mohammed, Abd El-Salam I.; Abdalla, Ashraf N.; Ragab, Ehab A. [Molecules, 2021, vol. 26, # 19]

40
[ 480-41-1 ]
[ 520-18-3 ]
[ 480-20-6 ]

Reference： [1]Journal of Agricultural and Food Chemistry,2018,vol. 66,p. 8272 - 8279

41
[ 480-41-1 ]
[ 520-18-3 ]

Reference： [1]Journal of Agricultural and Food Chemistry,2018,vol. 66,p. 8272 - 8279

42
[ 520-18-3 ]
[ 108-24-7 ]
3,4',5-tri-O-acetylkaempferol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91.8%	With 4-methylpiperidin at 100 - 140℃;	3.1 Example 3: Preparation of 8-isoprenyl-substituted apigenin 1) 2 g of apigenin, 3.3 to 5 equivalents of acetic anhydride, 2 to 4 times of 4-methylpiperidine, reacted at 100 to 140 ° C for 4 to 21 h, the product is IIa,The yield was 91.8%.

Reference： [1]Current Patent Assignee: GUANGDONG JINJUNKANG BIO TECH - CN109369748, 2019, A Location in patent: Paragraph 0036; 0037

43
[ 520-18-3 ]
[ 108-24-7 ]
C₁₉H₁₄O₈ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92.4%	With piperidine at 100 - 140℃;	1.1 Example 1: Preparation of 6,8-diisoprenyl-substituted apigenin 1) 2 g of apigenin, 2-2.4 times equivalent of acetic anhydride, 2-4 times of piperidine,The reaction is carried out at 100 to 140 ° C for 2 to 24 hours, and the product is IIa, and the yield is 92.4%

Reference： [1]Current Patent Assignee: GUANGDONG JINJUNKANG BIO TECH - CN109369748, 2019, A Location in patent: Paragraph 0026; 0027

44
[ 27200-12-0 ]
[ 520-18-3 ]

Reference： [1]Patent: CN109369593,2019,A

45
[ 520-18-3 ]
uridine 5'-diphospho-N-acetylglucosamine [ No CAS ]
kaempferol 3-O-N-acetylglucosamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With 3-O-glycosyltransferase from Scutellaria baicalensis In dimethyl sulfoxide at 45℃; for 4h; Enzymatic reaction; regiospecific reaction;

Reference： [1]Wang, Zilong; Wang, Shuang; Xu, Zheng; Li, Mingwei; Chen, Kuan; Zhang, Yaqun; Hu, Zhimin; Zhang, Meng; Zhang, Zhiyong; Qiao, Xue; Ye, Min [Organic Letters, 2019, vol. 21, # 7, p. 2241 - 2245]

46
[ 520-18-3 ]
[ 187661-86-5 ]
benzyl (E)-3-(4-(3,5,7-trihydroxy-4-oxo-4H-chromen-2-yl)phenoxy)but-2-enoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
23.6%	With potassium carbonate; triphenylphosphine; bis(dibenzylideneacetone)-palladium⁽⁰⁾ In N,N-dimethyl-formamide at 80℃; for 10h; Inert atmosphere; Sealed tube; regioselective reaction;	2.2.3. General Procedure for the Synthesis of Target Derivatives 3a-3i, 4a-4g, 5a-5e General procedure: Chrysin 2a (127.12 mg, 0.5 mmol), Pd(dba)2 (5.75 mg, 0.01 mmol), K2CO3 (138.21 mg, 1.0 mmol),PPh3 (13.11 mg, 0.05 mmol), allene (112.13 mg, 1.0 mmol), and anhydrous DMF (5 mL) were addedto a 30 mL tube under argon, which was then sealed. The resulting mixture was stirred at 80 °C for12 h. After completion, the reaction solution was cooled down to room temperature before 80 mLwater was added, followed by the addition of 1 N HCl aqueous solution at 0 °C, until the pH value reached 7. Ethyl acetate (100 mL) was added to the reaction solution and the organic layer was washed sequentially with a large amount of water (4 x 200 mL), and then brine, before being dried overanhydrous Na2SO4. The solvent was evaporated under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether-ethylacetate, 5:1) to give 3a (78.8 mg,43% yield). Compounds 3b-3i, 4a-4g, and 5a-5e were prepared according to similar procedures in which the double-substitution is a by product. The products 4a-4g were generated in a shorter time compared with the other products (within 10 h).

Reference： [1]Jin, Lu; Wang, Meng-Ling; Lv, Yao; Zeng, Xue-Yi; Chen, Chao; Ren, Hai; Luo, Heng; Pan, Wei-Dong [Molecules, 2019, vol. 24, # 9]

47
C₂₇H₂₉O₁₆^(1-)*Na⁽¹⁺⁾ [ No CAS ]
[ 492-61-5 ]
[ 520-18-3 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride In water at 90℃; for 5h;	2.4 Hydrolysis of 1-3 General procedure: Compounds 1-3 (10mg each) were separately dissolved in 1% aqueous NaHCO3 (10mL) and then heated at 90°C for 6h. To get the flavonoid glycosides which lose the monoterpenyl moiety, the reaction mixture was purified by Flash-ODS after cooling. Then 2mol/L HCl solution (2mL) was added to the sample solution and heated at 90°C for 5h (Fig. 2 ). When cooling, the mixture was neutralized with NaHCO3, and then dried by vacuum concentration to get the sample.

Reference： [1]Li, Rui; Wang, Qing; Zhao, Menghao; Yang, Peiming; Hu, Xiao; Ouyang, Danwei [Fitoterapia, 2019, vol. 137]

48
[ 520-18-3 ]
C₁₂H₉BrO [ No CAS ]
C₂₇H₁₈O₇ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
5.8%	With potassium carbonate In 1,4-dioxane at 80℃; for 24h;	3.1 Example 3: Preparation method of compound W1-W34 General procedure: Weigh 1 equivalent of B1-B34, 2 equivalents of kaempferol, 2 equivalents of anhydrous potassium carbonate In the reaction flask, a 1,4-dioxane dispersion raw material was added, and the reaction liquid was stirred at 80 ° C for 24 hours, and then the reaction was stopped. To the reaction solution, 0.6 mol/L of dilute hydrochloric acid was added to adjust the pH to a weak acidity, and then 10 ml of distilled water was added thereto, and the aqueous phase was extracted three times with ethyl acetate. The organic phase was collected and dried over anhydrous magnesium sulfate. , The crude product was purified by HW-40C gel column chromatography (mobile phase, Purification by thin layer chromatography using dichloromethane:methanol = 2:1) (developing agent, dichloromethane: methanol = 19:1) A pale yellow solid W1-W34 was obtained.

Reference： [1]Current Patent Assignee: TIANJIN MEDICAL UNIVERSITY - CN109988139, 2019, A Location in patent: Paragraph 0022-0023; 0024-0025

49
[ 520-18-3 ]
C₁₅H₆⁽²⁾H₄O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	Stage #1: kaempferol With [D]-sodium hydroxide; platinum on activated charcoal; water-d2 at 130℃; for 9h; Inert atmosphere; Stage #2: With formic acid at 130℃; for 1h; Inert atmosphere;	31 Example 31 Add 10 mg of kaempferol to 200 μL of heavy water to the reaction vessel.1mg Pt/C and 70μLdeuteriumSodium oxide solution,Filled with nitrogen and reacted at 130 ° C for 9 hours.Then, 70 μL of formic acid was added and reacted at 130 ° C for 1 hour.The reaction solution was collected and lyophilized to obtain a solid, which was dissolved in ethanol.The filtrate was collected by filtration and dried to obtain a deuterated kaempferol solid.Mass spectrometry(deuteriumFour main peaks)The yield was 62%.

Reference： [1]Current Patent Assignee: HUNAN NORMAL UNIVERSITY - CN109879847, 2019, A Location in patent: Paragraph 0116-0118

50
[ 520-18-3 ]
C₁₁H₇BrFNO [ No CAS ]
3-O-[(E)-4-(4-cyano-2-fluorophenyl)-2-oxobut-3-en-1-yl]kaempferol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
4.6%	With potassium carbonate In 1,4-dioxane at 80℃;	5.1.3 General procedure for the synthesis of compounds 4 and 8 General procedure: Target compounds 4 and 8 were semi-synthesized from kaempferol with α- bromine substituted ketos using an etherification reaction. A solution of the bromine substituted ketos (1.0eq) in 1,4-dioxane (5ml) was added to a mixture of kaempferol (1.2eq) and K2CO3 (1.2eq) in 1,4-dioxane (10ml; stirred for 90min while maintaining gentle reflux) and mixed for 30min. Stirring of the reaction mixture at 80°C was continued until TLC indicated that the starting material had disappeared (CH2Cl2: MeOH, 95:5). Under reduced pressure, the solvent was removed from the reaction mixture, water was added, 1M HCl was added to the aqueous phase for neutralization (to pH 7), and the reaction was extracted using ethyl acetate. The organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated. Gel-permeation chromatography (HW-40; CH2Cl2: MeOH, 1:1) and preparative-TLC were used to purify the crude product, which appeared as a yellow solid product.