* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference：
[1] Advanced Synthesis and Catalysis, 2001, vol. 343, # 8, p. 802 - 808
11
[ 56-45-1 ]
[ 534-03-2 ]
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[1] Chemical Communications, 2014, vol. 50, # 50, p. 6656 - 6659
[2] Chemistry - A European Journal, 2015, vol. 21, # 7, p. 3097 - 3107
12
[ 56-45-1 ]
[ 1068-84-4 ]
Reference：
[1] Chemistry Letters, 1980, p. 1545 - 1548
13
[ 1342309-23-2 ]
[ 17407-56-6 ]
[ 17407-55-5 ]
[ 312-84-5 ]
[ 56-45-1 ]
[ 20312-37-2 ]
[ 13748-90-8 ]
[ 3060-46-6 ]
[ 63-91-2 ]
[ 31321-74-1 ]
[ 673-06-3 ]
Reference：
[1] Journal of Natural Products, 2011, vol. 74, # 10, p. 2137 - 2142
14
[ 1342309-24-3 ]
[ 17407-56-6 ]
[ 17407-55-5 ]
[ 312-84-5 ]
[ 56-45-1 ]
[ 20312-37-2 ]
[ 13748-90-8 ]
[ 3060-46-6 ]
[ 63-91-2 ]
[ 31321-74-1 ]
[ 673-06-3 ]
Reference：
[1] Journal of Natural Products, 2011, vol. 74, # 10, p. 2137 - 2142
15
[ 56-45-1 ]
[ 454-29-5 ]
[ 348-67-4 ]
Reference：
[1] Agricultural and Biological Chemistry, 1984, vol. 48, # 1, p. 143 - 148
16
[ 56-41-7 ]
[ 77287-34-4 ]
[ 56-45-1 ]
[ 70-47-3 ]
[ 471-46-5 ]
Reference：
[1] Bulletin of the Chemical Society of Japan, 2014, vol. 87, # 11, p. 1208 - 1215
17
[ 56-41-7 ]
[ 77287-34-4 ]
[ 56-45-1 ]
[ 70-47-3 ]
[ 56-40-6 ]
Reference：
[1] Bulletin of the Chemical Society of Japan, 2014, vol. 87, # 11, p. 1208 - 1215
18
[ 101301-51-3 ]
[ 56-45-1 ]
[ 70-47-3 ]
[ 56-40-6 ]
[ 71-00-1 ]
Reference：
[1] Chemical and Pharmaceutical Bulletin, 1985, vol. 33, # 8, p. 3205 - 3217
19
[ 56-45-1 ]
[ 75-36-5 ]
[ 5147-00-2 ]
Reference：
[1] Chemical Research in Toxicology, 2001, vol. 14, # 1, p. 54 - 61
[2] Patent: CN107501127, 2017, A, . Location in patent: Paragraph 0014; 0027
20
[ 56-45-1 ]
[ 72-89-9 ]
[ 5147-00-2 ]
Reference：
[1] Phytochemistry, 2005, vol. 66, # 12, p. 1407 - 1416
[2] Biochimica et Biophysica Acta - Proteins and Proteomics, 2014, vol. 1844, # 10, p. 1741 - 1748
21
[ 56-45-1 ]
[ 64-19-7 ]
[ 5147-00-2 ]
Reference：
[1] Journal of the American Chemical Society, 1956, vol. 78, p. 1367
[2] Journal of the American Chemical Society, 1954, vol. 76, p. 2881,2882
22
[ 67-56-1 ]
[ 56-45-1 ]
[ 7691-28-3 ]
Yield
Reaction Conditions
Operation in experiment
65%
Stage #1: With bromic acid; potassium bromide; sodium nitrite In water at -10 - 20℃; Stage #2: With bromic acid In water at 65℃; for 48 h;
[1496] Step 2: methyl 2-bromo-3-hydroxypropanoate[1497] To a solution of L-serine (5.0 g, 47.6 mmol), a 48 w/wpercent bromic acid solution (13.0 mL, 109.5 mmol), and potassium bromide (20.0 g, 157.1 mmol) in water (44.0 mL) was added portionwise sodium nitrite (6.0 g, 80.9 mmol) at -10 ℃. The reaction mixture was stirred at room temperature overnight. The reaction mixture was saturated with sodium chloride and then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and then evaporated. The residue was dissolved in methanol (50.0 mL) and then 48 w/wpercent bromic acid (0.2 mL) was added thereto. The reaction mixture was stirred at 65 ℃ for 2 days and then concentrated under reduced pressure to discard excess methanol. The resulting dark yellow residue was dissolved in dichloromethane (100.0 mL) and then washed with a saturated sodium hydrogen carbonate solution (50.0 mL) and brine. The organic layer was dried over anhydrous sodium sulfate, filtered, and then evaporated. The residue was dried under reduced pressure to give 5.7 g of the titled compound (Yield: 65percent).[1498] 1H NMR (CDCl3, 400 MHz) δ 4.36(t, 1H), 4.01-4.08(m, 1H), 3.93-3.97(m, 1H), 3.82(s, 3H), 2.56(t, 1H)
65%
Stage #1: With bromic acid; potassium bromide; sodium nitrite In water at -10 - 20℃; Stage #2: at 65℃; for 48 h;
Step 2: methyl 2-bromo-3-hydroxypropanoate To a solution of L-serine (5.0 g, 47.6 mmol), a 48 w/w percent bromic acid solution (13.0 mL, 109.5 mmol), and potassium bromide (20.0 g, 157.1 mmol) in water (44.0 mL) was added portionwise sodium nitrite (6.0 g, 80.9 mmol) at -10° C. The reaction mixture was stirred at room temperature overnight. The reaction mixture was saturated with sodium chloride and then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and then evaporated. The residue was dissolved in methanol (50.0 mL) and then 48 w/w percent bromic acid (0.2 mL) was added thereto. The reaction mixture was stirred at 65° C. for 2 days and then concentrated under reduced pressure to discard excess methanol. The resulting dark yellow residue was dissolved in dichloromethane (100.0 mL) and then washed with a saturated sodium hydrogen carbonate solution (50.0 mL) and brine. The organic layer was dried over anhydrous sodium sulfate, filtered, and then evaporated. The residue was dried under reduced pressure to give 5.7 g of the titled compound (Yield: 65percent). 1H NMR (CDCl3, 400 MHz) δ 4.36 (t, 1H), 4.01-4.08 (m, 1H), 3.93-3.97 (m, 1H), 3.82 (s, 3H), 2.56 (t, 1H)
Reference：
[1] Journal of the American Chemical Society, 1993, vol. 115, # 4, p. 1264 - 1270
29
[ 56-45-1 ]
[ 6027-13-0 ]
[ 56-88-2 ]
Reference：
[1] Methods in Enzymology, Bd. 5 <New York 1962> S. 943,
[2] The Enzymes, Bd. 5 <New York 1961> S. 564, 567,
[3] Biochimica et Biophysica Acta - Proteins and Proteomics, 2010, vol. 1804, # 7, p. 1424 - 1431
[4] Antioxidants and Redox Signaling, 2018, vol. 28, # 4, p. 311 - 323
30
[ 56-45-1 ]
[ 6027-13-0 ]
[ 56-88-2 ]
[ 7732-18-5 ]
Reference：
[1] Journal of Biological Chemistry, 2012, vol. 287, # 52, p. 43464 - 43471
Reference：
[1] Journal of Organic Chemistry, 1986, vol. 51, # 8, p. 1175 - 1179
33
[ 67-56-1 ]
[ 56-45-1 ]
[ 24424-99-5 ]
[ 2766-43-0 ]
Reference：
[1] Organic Letters, 2004, vol. 6, # 1, p. 19 - 22
[2] Tetrahedron, 1996, vol. 52, # 36, p. 11673 - 11694
[3] Journal of Organic Chemistry, 2003, vol. 68, # 1, p. 50 - 54
34
[ 56-45-1 ]
[ 24424-99-5 ]
[ 2766-43-0 ]
Reference：
[1] Journal of Organometallic Chemistry, 2003, vol. 674, # 1-2, p. 24 - 31
35
[ 186581-53-3 ]
[ 56-45-1 ]
[ 24424-99-5 ]
[ 2766-43-0 ]
Reference：
[1] Journal of Organic Chemistry, 1996, vol. 61, # 16, p. 5418 - 5424
36
[ 64-17-5 ]
[ 56-45-1 ]
[ 26348-61-8 ]
Reference：
[1] Farmaco, 2004, vol. 59, # 8, p. 645 - 649
[2] Polymer, 2010, vol. 51, # 12, p. 2479 - 2485
[3] Journal of the American Chemical Society, 1957, vol. 79, p. 3236,3238
[4] Pharmaceutical Chemistry Journal, 1986, vol. 20, # 9, p. 632 - 636[5] Khimiko-Farmatsevticheskii Zhurnal, 1986, vol. 20, # 9, p. 1064 - 1068
[6] Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 2, p. 750 - 758
37
[ 6378-11-6 ]
[ 56-45-1 ]
[ 26348-61-8 ]
Reference：
[1] Chemistry and Biodiversity, 2018, vol. 15, # 5,
38
[ 56-45-1 ]
[ 75-36-5 ]
[ 66638-22-0 ]
Reference：
[1] Journal of Organic Chemistry, 2003, vol. 68, # 7, p. 2652 - 2667
39
[ 64-17-5 ]
[ 56-45-1 ]
[ 3940-27-0 ]
Yield
Reaction Conditions
Operation in experiment
93.4%
for 11 h; Cooling with ice; Reflux
In 100 ml of ethanol is added in three-mouth bottle 40 ml, under the condition of the mechanical stirring ice-water bath, slow adds by drops two chlorine Asia sulphone 5.4 ml, after dripping, continue to stir 1h, (II) 6.00g the L-serine (57mmol) inputs in three-mouth bottle, heating reflux reaction, the reaction time is 10h rear, reduced pressure distillation to remove the solvent, to obtain L-serine methyl ester hydrochloride (III) 9.05g, yield 93.4percent
Reference：
[1] Patent: CN105777611, 2016, A, . Location in patent: Paragraph 0052; 0053
40
[ 56-45-1 ]
[ 100-51-6 ]
[ 60022-62-0 ]
Yield
Reaction Conditions
Operation in experiment
54%
Stage #1: With toluene-4-sulfonic acid In tetrachloromethaneReflux Stage #2: With hydrogenchloride In water
a) A 250-mL flask was charged with H-l-Ser-OH (15) (15.00 g, 0.14 mol) and p-TsOH (29.30 g, 0.15 mol) in a mixture of BnOH (70 mL) and CCl4 (70 mL). The reaction mixture was heated at reflux under Dean-Stark conditions overnight (7 mL H2O removed). CCl4 was removed by evaporation under reduced pressure. DCM (50 mL) was added to the mixture and the resulting solution was washed with sat. NaHCO3 (3 x 50 mL). The organic phase was extracted with 1 M HCl (3 x 50 mL). The aqueous solution was concentration in vacuo and dried to yield H-Ser-OBn HCl (17.52 g, 54percent) as colorless crystals. mp 169-171 °C. LC-MS m/z: 196.15 [M+1].b) Boc-Phe-OH (2.92 g, 11.00 mmol) was dissolved in DMF (50 mL) in a 100-mL dry flask. DIPEA (1.88 mL, 11.00 mmol), EDCI (1.95 mL, 11.00 mmol), and HOBt (1.49 g, 11.00 mmol) were added to the reaction mixture. After the solution was stirred for 5 min at rt, H-Ser-OBn (2.31 g, 10.00 mmol) was added and stirring was continued overnight. The reaction mixture was diluted with 150 mL Et2O and washed with 1M HCl (2 x 100 mL), brine (100 mL), sat. NaHCO3 (2 x 100 mL), and brine (100 mL). The organic phase was dried over anhydrous MgSO4 and concentrated in vacuo. Flash chromatography purification using a mobile phase of 1:1 EtOAc, hexane afforded 16 (2.08 g, 78percent) as a colorless oil.
52.3%
Stage #1: for 12 h; Heating / reflux Stage #2: With sodium hydrogencarbonate In water Stage #3: With hydrogenchloride In dichloromethane at 0℃; for 1.5 h;
To prepare L-Serine benzyl ester hydrichloride sale (2), L-Serine (5.25 g) and p- toluenesulfonic acid (0.6 g) were suspended in benzyl alcohol (25 mL) and dissolved by heating on an oil bath using the Dean and Stark apparatus. Benzene (25 mL) was added and refluxed for 12 h; the reaction was cooled to RT and concentrated. The sample was then redissolved in 5percent NaHCO3 solution and extracted with i-PrOH/CHCl3 (1:4, 3x50 mL), dried over MgSO4, filtered and evaporated to a residue. The residue was dissolved in 125 mL of CH2Cl2 and HCl gas bubbled into the solution at O0C for 30 minutes followed by stirring for 1 h. The precipitated white solid was washed with diethyl ether and recrystallized from i-PrOH/CH3OH (13:1) according to the procedure of Holden et al. (2002) J. Org. Chem. 67, 5913-5918. Yield 52.3percent (over two steps), m.p. = 170-1710C, [a]233D = -4.35° (c = 1.1), 1H NMR (DMSO, 500 MHz) d 3.87 (d, J= 3 Hz, 2H), 4.14 (t, J= 3 Hz, IH), 5.21 ( s, 2H), 5.70 (IH, broad), 7.36 (m, 5H); 13C NMR (DMSO, 500 MHz) d 54.55 (β-CH2), 59.54 (a-CH), 66.90 (CH2Ph), 127.90 (CH), 128.19 (2CH), 128.42 (2CH), 135.31 (C, q), and 167.95 (-COO-).
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 15, p. 4597 - 4601
[2] Patent: WO2007/55698, 2007, A1, . Location in patent: Page/Page column 8-9
[3] Journal of Carbohydrate Chemistry, 2010, vol. 29, # 4, p. 181 - 206
[4] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 17, p. 6220 - 6229
41
[ 15861-24-2 ]
[ 56-45-1 ]
[ 139393-02-5 ]
Reference：
[1] Journal of the American Chemical Society, 2017, vol. 139, # 31, p. 10769 - 10776
[2] Angewandte Chemie - International Edition, 2016, vol. 55, # 38, p. 11577 - 11581[3] Angew. Chem., 2016, vol. 128, p. 11749 - 11753,5
42
[ 399-52-0 ]
[ 56-45-1 ]
[ 16626-02-1 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 16, p. 4508 - 4510
[2] Chemical Communications, 2011, vol. 47, # 8, p. 2321 - 2323
[3] ChemBioChem, 2011, vol. 12, # 9, p. 1391 - 1395
[4] Amino Acids, 2013, vol. 44, # 5, p. 1329 - 1336
[5] ChemCatChem, 2014, vol. 6, # 5, p. 1270 - 1276
[6] Proceedings of the National Academy of Sciences of the United States of America, 2015, vol. 112, # 47, p. 14599 - 14604
43
[ 56-45-1 ]
[ 100-52-7 ]
[ 79-04-9 ]
[ 106973-37-9 ]
Reference：
[1] Journal of Medicinal Chemistry, 2009, vol. 52, # 21, p. 6527 - 6530
44
[ 2380-86-1 ]
[ 56-45-1 ]
[ 13567-14-1 ]
Reference：
[1] Proceedings of the National Academy of Sciences of the United States of America, 2015, vol. 112, # 47, p. 14599 - 14604
45
[ 56-45-1 ]
[ 51887-89-9 ]
Reference：
[1] Patent: US6372941, 2002, B1, . Location in patent: Example 6
[2] Patent: US6372941, 2002, B1, . Location in patent: Example 6
[3] Patent: US6372941, 2002, B1, . Location in patent: Example 6
[4] Patent: US6372941, 2002, B1, . Location in patent: Example 1-2
[5] Chemistry - A European Journal, 2018,
46
[ 1006-94-6 ]
[ 56-45-1 ]
[ 25197-96-0 ]
Reference：
[1] Angewandte Chemie - International Edition, 2016, vol. 55, # 38, p. 11577 - 11581[2] Angew. Chem., 2016, vol. 128, p. 11749 - 11753,5
47
[ 4837-90-5 ]
[ 56-45-1 ]
[ 406938-53-2 ]
Reference：
[1] Journal of the American Chemical Society, 2013, vol. 135, # 5, p. 1895 - 1902
[2] Angewandte Chemie - International Edition, 2018, vol. 57, # 23, p. 6830 - 6833[3] Angew. Chem., 2018, vol. 130, # 23, p. 6946 - 6949,4
48
[ 17422-33-2 ]
[ 56-45-1 ]
[ 33468-35-8 ]
Reference：
[1] Journal of the American Chemical Society, 2017, vol. 139, # 31, p. 10769 - 10776
[2] Chemistry - A European Journal, 2011, vol. 17, # 15, p. 4183 - 4194
[3] Amino Acids, 2013, vol. 44, # 5, p. 1329 - 1336
[((8R,11S)-11-[(2S,3R)-1-((S)-2-Amino-propionyl)-3-hydroxy-pyrrolidine-2-carbonyl]-amino}-2,4-dihydroxy-10,14-dioxo-5,7,8,9,10,11,12,14-octahydro-13-oxa-6-thia-9-aza-benzocyclododecene-8-carbonyl)-amino]-acetic acid[ No CAS ]
(S)-2-[((8R,11S)-11-[(2S,3R)-1-((S)-2-Amino-propionyl)-3-hydroxy-pyrrolidine-2-carbonyl]-amino}-2,4-dihydroxy-10,14-dioxo-5,7,8,9,10,11,12,14-octahydro-13-oxa-6-thia-9-aza-benzocyclododecene-8-carbonyl)-amino]-propionic acid[ No CAS ]
(S)-4-Amino-5-[(2S,3R)-2-((8R,11S)-8-carbamoyl-2,4-dihydroxy-1-methyl-10,14-dioxo-5,7,8,9,10,11,12,14-octahydro-13-oxa-6-thia-9-aza-benzocyclododecen-11-ylcarbamoyl)-3-hydroxy-pyrrolidin-1-yl]-5-oxo-pentanoic acid[ No CAS ]
(S)-4-{(S)-2-[(S)-2-((S)-2-Amino-3-hydroxy-propionylamino)-3-methyl-butyrylamino]-3-phosphonooxy-propionylamino}-4-((S)-1-carboxy-ethylcarbamoyl)-butyric acid[ No CAS ]
With acetic acid; In Petroleum ether; at 20 - 30℃;
Dissolve 105 g (1.0 mol) of L-serine solid in 525 to 5250 ml (9.2 to 92.0 mol) acetic acid solution.Stir to fully dissolve the solid L-serine,71 ml (1.0 mole) of acetyl chloride was added dropwise at 20-30C.Add 30-60 minutes.The end of the drip,Stir for 1-3 hours at 20-30C.The reaction solution was added to 1050 to 10,500 ml (7.0 to 70.0 parts by weight) of petroleum ether solution.O-acetyl-L-serine precipitation,filter,The intermediate O-acetyl-L-serine was dried.
With serine acetyltransferase from Brucella abortus; In aq. acetate buffer; at 20℃; for 0.0333333h;Enzymatic reaction;Kinetics;
BaSAT activity was calculated by monitoring the decrease in absorbance at 232 nm (A232) due to the breakage of the thioester bond of acetyl coenzyme A using an Ultrospec 2100pro spectrophotometer (GE Healthcare). For this assay, the reaction mixture contained 50 mM Tris-HCl (pH 8.0), 0.1 mM acetyl-CoA, and 2.5 mug of BaSAT. The reaction was started by adding serine, and the absorbance was monitored every 2 s starting from zero. To calculate Km for the binding of serine, the amino acid was added in varying concentrations from 10 to 500 muM, keeping the concentration of acetyl CoA constant at 0.1 mM, and the reaction was carried out at room temperature for 2 min. The Km and the Vmax values were calculated using the Michaelis-Menten curve. Km was similarly calculated for acetyl Co-A, by varying acetyl Co-A from 10 to 400 muM and keeping the concentration of serine constant at 120 muM. Kinetic studies were performed in triplicate using 7-8 different concentrations of both serine and acetyl CoA. To measure the inhibition by l-cysteine, similar reactions were repeated using two different concentrations of cysteine, at 5 and 10 muM. The velocity of the reaction was calculated from the linear part of the time curve (30 s).
With sulfuric acid; at 25℃; for 2h;Molecular sieve;
General procedure: 10 mmol of amino acid, 4 g of molecular sieves and 20 mL of MTBE was taken in a 50 mL round bottom flask fitted with a septum and cooled to 25 C. To this solution 30 mmol of sulfuric acid was added very slowly using syringe. Reaction was carried out at 25 C for given reaction time as shown in Table 5. Reaction was slowly quenched in to 25 mL of saturated aqueous solution of sodium bicarbonate. Organic layer was separated, and aqueous layer was extracted twice with hexane. Combined organic layer was washed with water, dried over sodium sulphate and the solvent was removed by distillation.
(S)-2-Amino-3-hydroxypropanoic acid (1 g, 9.43 mmol) was suspended in AcOtBu (30 mL), HClO4 (0.9 mL, 70% in water, 10.4 mmol) was added and the mixture was stirred for 4 h. After that time, the solution was poured onto a saturated NaHCO3 aqueous (100 mL) and stirring for 0.5 h. Then, the mixture was partitioned between water and CH2Cl2, the aqueous phase was extracted with CH2Cl2 and the organic layer was washed with brine and dried over MgSO4, filtered and concentrated in vacuo to afford 1.65 g of (S)-tert-butyl 2-amino-3-tert-butoxypropanoate (23) as a colorless oil in a 80% yield: [alpha]31D [alpha]D31 : -5.0 (CHCl3, c = 4.71). 1H NMR (300 MHz, CDCl3) deltaH: 1.15 (s, 9H); 1.45 (s, 9H); 1.97 (br s, 2H); 3.46 (br s, 1H); 3.51-3.66 (m, 2H). 13C NMR (300 MHz, CDCl3) deltaC: 27.55; 28.20; 55.69; 63.99; 72.98; 81.12; 173.39. (+)-LREIMS m/z (%): 218 ([M+H]+, 100); (+)-HRESIMS: m/z 218.1721 [M+H]+ (calcd. for C11H24NO3, 218.1756)
2 g
With perchloric acid; In water; at 20℃; for 4h;
The L - serine 1 H (1 g, 9.43 mmol) dissolved in 30 ml tert-butyl acetate in, then adding 70% aqueous solution of perchloric acid (0.9 ml, 10.4 mmol) stirring at the room temperature reaction 4 h after, TLC detection after the reaction is complete, the concentrated add saturated sodium bicarbonate, extracted with ethyl acetate two times after adding anhydrous sodium sulfate for drying the organic phase, concentrated under reduced pressure to obtain transparent liquid 1 J product 2 g.
With tryptophan synthase cell lysate; In aq. phosphate buffer; at 37℃; for 48h;pH 7.8;Enzymatic reaction;
General procedure: l-Serine 2 (0.262g, 2.5mmol, 1.25equiv) was dissolved in KH2PO4 reaction buffer (0.1M, pH 7.8, 95mL). A solution of <strong>[169674-01-5]<strong>[169674-01-5]5,6-difluoro-1H-indol</strong>e</strong> 8 (0.306g, 2.0mmol, 1.0equiv) in methanol (5mL) was added to the flask containing the reaction buffer with vigorous stirring. Tryptophan synthase cell lysate was thawed in a 37C water bath, then stored at 0C. The cell lysate (3mL) was stored in a cellulose dialysis bag and added to the reaction flask. The biotransformation was carried out at 37C, shaking at 180rpm for 2 days. The aqueous layer was collected and washed with ethyl acetate (2×50mL). The aqueous layer was concentrated to half its volume, then purified on C18 silica. The aqueous layer was loaded onto 30g C18 silica, which was then washed with 200mL water before elution of the product in methanol. The methanolic fractions were collected and the solvent was removed in vacuo. The residue was dissolved in water (50mL) and lyophilised to give l-5,6-difluorotryptophan 8 (245mg, 51%) as a white solid; [alpha]D -12.4 (c 0.51, MeOH); 1H NMR (500MHz, D2O) delta=3.23 (1H, dd, J(H,H)=15.5, 7.1Hz, CHAHB), 3.28 (1H, dd, J(H,H)=15.5, 5.4Hz, CHAHB), 4.18 (1H, dd, J(H,H)=6.9, 5.5Hz, CH), 7.19 (2H, overlapping m, ArH), 7.28 (1H, dd, J(H,F)=11.2, 7.7Hz, ArH); 13C NMR (125MHz, D2O) delta=25.6 (CH2), 53.3 (CH), 99.5 (d, J(C,F)=21.7Hz, CH), 104.4 (d, J(C,F)=19.5Hz, CH), 106.6 (d, J(C,F)=5.6Hz, C), 121.7 (d, J(C,F)=8.1Hz, C) 126.4 (d, J(C,F)=3.5Hz, CH), 131.2 (d, J(C,F)=10.9Hz, C), 145.8, (dd, J(C,F)=198.6, 15.0Hz, CF), 147.6 (dd, J(C,F)=200.0, 15.3Hz, C), 172.0 (CO); 19F{1H} NMR (470MHz, D2O) delta=-148.4 (d, J(F,F)=21.1Hz), -144.9 (d, J(F,F)-21.1Hz); HRMS (ESI): m/z calcd for C11H11F2N2O2+ [M+H]+: 241.0783; found 241.0782.
With ammonium hydroxide; In water; at 20℃; for 6h;pH 9.7 - 9.8;Green chemistry; Enzymatic reaction;
At first, 6.30 g (60.0 mmol) of l-serine and 2.25 g (15.0 mmol) of d-PGA were suspended in water and the pH was adjusted to 9.70 with NH4OH 25percent, making an overall volume of 230 mL. Next, 6.01 g of immobilized penicillin acylase was added at room temperature. Three further portions of d-PGA (2.25 g, 15.0 mmol) were added, with a 1.5-hour interval each, at which the pH was readjusted to 9.8 with the same base. After 6 hours, the enzyme was filtered and a turbid mixture was obtained. The pH was adjusted to 5.6 with H2SO4 (6 M). The mixture was left stirring for 4 days, after which precipitation occurred. The solid formed was filtered, washed with petroleum ether 40-60, dried, and 200 mg was obtained. The mixture was kept stirring for a period of 50 days and more precipitate was formed. This was collected, following the same procedure, after which 1.17 g was obtained in the second fraction, affording a total yield of 10percent. The product was isolated pure. Mp: 224-226 °C (d). [alpha]D20 = -68.9 (c 1, 2.5 M HCl). 1H NMR (300 MHz, D2O+DCl): delta = 7.49-7.51 (m, aromatic protons), delta = 5.22 (s, CHNH2), delta = 4.54 (t, J = 4.5 Hz, CHCH2OH), delta = 3.861, delta = 3.86, 3.73 (m, m, J1 = 3.9 Hz, J2 = 11.7 Hz, CHCH2OH); 13C NMR (75 MHz, D2O+DCl): delta = 174.5, 170.3 (C=O), delta = 133.3, 132.0, 131.3, 129.6 (Ar); delta = 62.26 CH2OH, delta = 58.08, 56.55 (Calpha).
[Ru(4,4'bis(methoxycarbonyl)-2,2'-bipyridine)2(L-serine)]NO3[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
46%
General procedure: [RuCl2(p-cymene)]2 (0.12 g, 0.20 mmol), glycine (0.03 g,0.40 mmol) and potassium tert-butoxide (0.05 g, 0.40 mmol) wereadded to dry methanol (40 mL), and the resulting mixture wasrefluxed for 30 min under argon atmosphere. AgNO3 (0.14 g,0.80 mmol) and dcmb (0.23 g, 0.85 mmol) were then added andthe reaction mixture was refluxed for additional 14 h in the dark.The reaction mixture was cooled to room temperature and filteredthrough a fine porosity frit to remove precipitated AgCl andexceeding dcmb. The filtrate was evaporated to dryness, and theresidue was recrystallized from a mixture of chloroform and hexane(v/v = 2:1), and dried in a vacuum to afford complex 3 as deepblue powder in a yield of 0.16 g (50percent).
With thionyl chloride; for 11h;Cooling with ice; Reflux;
In 100 ml of ethanol is added in three-mouth bottle 40 ml, under the condition of the mechanical stirring ice-water bath, slow adds by drops two chlorine Asia sulphone 5.4 ml, after dripping, continue to stir 1h, (II) 6.00g the L-serine (57mmol) inputs in three-mouth bottle, heating reflux reaction, the reaction time is 10h rear, reduced pressure distillation to remove the solvent, to obtain L-serine methyl ester hydrochloride (III) 9.05g, yield 93.4%
With tryptophan synthase cell lysate; In aq. phosphate buffer; at 37℃; for 48h;pH 7.8;Enzymatic reaction;
General procedure: l-Serine 2 (0.262g, 2.5mmol, 1.25equiv) was dissolved in KH2PO4 reaction buffer (0.1M, pH 7.8, 95mL). A solution of 5,6-difluoro-1H-indole 8 (0.306g, 2.0mmol, 1.0equiv) in methanol (5mL) was added to the flask containing the reaction buffer with vigorous stirring. Tryptophan synthase cell lysate was thawed in a 37C water bath, then stored at 0C. The cell lysate (3mL) was stored in a cellulose dialysis bag and added to the reaction flask. The biotransformation was carried out at 37C, shaking at 180rpm for 2 days. The aqueous layer was collected and washed with ethyl acetate (2×50mL). The aqueous layer was concentrated to half its volume, then purified on C18 silica. The aqueous layer was loaded onto 30g C18 silica, which was then washed with 200mL water before elution of the product in methanol. The methanolic fractions were collected and the solvent was removed in vacuo. The residue was dissolved in water (50mL) and lyophilised to give l-5,6-difluorotryptophan 8 (245mg, 51%) as a white solid.
With hydrogenchloride; In water; at 110℃; for 10h;Sealed tube;
To 1.0 mg of cichorinotoxin was added 1.0 mL of 6 N HCl, andthe mixture was frozen at -30 C and degassed under a highvacuum pump. The glass vessel was sealed and heated at110 C for 5 h, 10 h and 22 h to obtain the hydrolysates, each of which were concentrated to dryness. The residues were evaluatedusing an amino acid analyzer. Marfey?s method was employedto determine the stereochemistry of each of the aminoacids. The dried hydrolysates obtained by heating for 10 h weredissolved in 140 muL of H2O. To 25 muL of the solution wereadded 1% Marfey?s reagent ((1-fluoro-2,4-dinitro-5-fluorophenyl)-L-alaninamide, 1.8 muM) dissolved in acetone and 10 muLof 1 M NaHCO3 (10 muM). The solution was heated at 35 C for1 h, then 2 N aq HCl was added to quench the reaction, and thenit was concentrated to dryness. The residues were dissolved inDMSO and subjected to reversed-phase HPLC (C18) using amobile phase composed of 13% CH3CN/87% 50 mM triethylaminephosphate. Amino acid compositions of naturalcichorinotoxin (not Marfey?s derivatives) were analyzed byHitachi Keisoku Service Ltd (Tokyo)
(S)-1-carboxy-2-hydroxyethan-1-aminium ((2R,3S,4R,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl phosphate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
83%
In water;pH 3.22 - 3.8;Inert atmosphere; Cooling with ice;
A 100 mL 3N RBF was charged with NMN (0.5 g, 1.492 mmol, 1.0 eq) and 25 ml of distilled deionised water and mixed to form a solution under nitrogen. This solution was cooled using an ice/water hath (pH of solution ==: 3.22). To this solution was then added dropwise 14.92 ml of 0.1M L-Serine solution slowly via syringe so as to prevent the temperature from increasing. After this addition the pH was 3.8. The mixture was transferred to a 250ml, RBF and the flask was then removed and the colourless solution frozen using liquid nitrogen. While the flask was frozen it was connected to the freeze dryer. This will slowly remove water. Once dried the product is rendered as a colourless to faint yellow solid (hygroscopic). Yield: 546.8 mg (83%) Melting point: 71 C (degradation), outgassing at 101 C. Analytical data. -NMR (400 MHz, D?O) 6 = 9.50 (s, 1H), 9.30 (d, H i), 8.93 (d, 1 1 1 ). 8.30 (app t, 1H), 6.21 (d, H I). 4.65 (p, 1H), 4.57 (t H I ), 4.46 (m, 1 1 1 ). 4.32 (dq, H i), 4.15 (dq, H i ), 3.9 (m, 211), 4.8 (t, H i ) ppm.
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