* 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] Bioscience, Biotechnology and Biochemistry, 2018, vol. 82, # 4, p. 724 - 731
6
[ 67-56-1 ]
[ 1447695-69-3 ]
[ 39994-75-7 ]
[ 6306-52-1 ]
[ 60667-85-8 ]
[ 18598-74-8 ]
[ 18598-63-5 ]
[ 2133-40-6 ]
Reference:
[1] Journal of Natural Products, 2013, vol. 76, # 7, p. 1388 - 1391
7
[ 67-56-1 ]
[ 1447695-69-3 ]
[ 39994-75-7 ]
[ 6306-52-1 ]
[ 60667-85-8 ]
[ 18598-74-8 ]
[ 18598-63-5 ]
[ 2133-40-6 ]
Reference:
[1] Journal of Natural Products, 2013, vol. 76, # 7, p. 1388 - 1391
8
[ 67-56-1 ]
[ 52-89-1 ]
[ 18598-63-5 ]
Yield
Reaction Conditions
Operation in experiment
85.9%
Stage #1: at 20℃; for 1 h; Cooling with ice; Inert atmosphere Stage #2: at 20℃; for 4 h; Reflux
Under ice-bath condition, 3 ml SOCl2 was added dropwise to 35 ml methanol in the presence of nitrogen atmosphere. Afterward, the solution was stirred at room temperature for 1 h, then 1 g Cys·HCl·H2O was added in batches to the solution. And the mixture solution reacted at room temperature for 3 h, and then refluxed for 1 h. Removing the volatile component and solvent, the residue was recrystallized with CH3OH-CH2Cl2, and 0.84 g white solid was obtained with 85.9percent yield. IR (KBr, cm-1): 3040.4 (s, NH2), 1709.7 (s, C=O), 2580 (w, SH). 1H NMR (D2O, TMS, ppm); δ 4.453 (t, 1H, CH, J = 5.2 Hz), 3.871 (s, 3H, CH3), 3.164 (t, 2H, CH2, J = 6.4 Hz). Elemental Anal. Calcd for C4H10NO2SCl: C, 27.99; H, 5.87; N, 8.16percent. Found: C, 28.11; H, 6.01; N, 8.08percent.
Reference:
[1] European Journal of Medicinal Chemistry, 2014, vol. 74, p. 199 - 215
[2] Journal of Organic Chemistry, 2013, vol. 78, # 9, p. 4270 - 4277
[3] Tetrahedron Asymmetry, 2000, vol. 11, # 21, p. 4255 - 4261
[4] Journal of the American Chemical Society, 2008, vol. 130, # 15, p. 5052 - 5053
[5] European Journal of Medicinal Chemistry, 2012, vol. 55, p. 176 - 187,12
9
[ 67-56-1 ]
[ 52-90-4 ]
[ 18598-63-5 ]
Yield
Reaction Conditions
Operation in experiment
100%
With thionyl chloride In methanol for 3 h; Reflux; Inert atmosphere
General procedure: These compounds 11a-f were prepared using the generalmethod described by Gududuru et al. [35].Thionyl chloride (8.3 mL, 110 mmol) was added dropwise underan atmosphere of argon to a solution of L-cysteine (8) (9.00 g,74 mmol) in 150mL MeOH. The reaction mixture was refluxed for3 h then evaporated in vacuo, then co-evaporated with toluene(2 5 mL) to afford the hydrochloride salt of the methyl ester of Lcysteine(9) as white solid. One-sixth of this material (9)(12.4 mmol) was dissolved in water/ethanol (1:1) (15 mL). Sodiumhydrogen carbonate (1.14 g, 13.6 mmol) was added and, after10 min, the aromatic aldehyde (10a-f) (12.38 mmol) was added andthe reaction mixture was stirred for 14 h. The ethanol was evaporatedin vacuo and the aqueous residue was extracted with DCM(50 mL). The organic layer was washed with water (25 mL), driedover Na2SO4, filtered and evaporated in vacuo to afford the crudeproducts 11a-f.
96%
at 0℃; for 2 h; Reflux
General procedure: Acetyl chloride (1.6 mL, 22 mmol) was added to MeOH (100 mL), and the solution was cooled to 0°C. The solution was stirred for 5 min. Amino acid (L-serine, D-serine, L-cysteine, D-cysteine, L-2,3-diaminopropionic acid, and D-2,3-diaminopropionic acid) (20 mmol) was then added to the acetyl chloride solution in methanol (MeOH), and the solution was heated to reflux for 2 h, then cooled to room temperature.The reaction was evaporated under reduced pressure and gavea colorless solid. The solid was washed with CH2Cl2 (20 mL)to give amino acid methyl ester hydrochloride (2d–f, 2d–f)as a white solid. The yields of 2d, d, e, e, f and f were 95percent,96percent, 94percent, 96percent, 95percent, 95percent, respectively.
Reference:
[1] European Journal of Medicinal Chemistry, 2018, vol. 157, p. 462 - 479
[2] Chemical and Pharmaceutical Bulletin, 2015, vol. 63, # 1, p. 33 - 37
[3] Bulletin of the Korean Chemical Society, 2017, vol. 38, # 1, p. 54 - 62
[4] Canadian Journal of Chemistry, 1990, vol. 68, # 8, p. 1408 - 1419
[5] Tetrahedron Letters, 1989, vol. 30, # 9, p. 1041 - 1044
[6] Journal of the American Chemical Society, 1992, vol. 114, # 12, p. 4500 - 4514
[7] Journal of the American Chemical Society, 2008, vol. 130, # 30, p. 9642 - 9643
[8] Magnetic Resonance in Chemistry, 2008, vol. 46, # 10, p. 986 - 989
[9] Journal of the American Chemical Society, 2009, vol. 131, # 45, p. 16346 - 16347
[10] Journal of the American Chemical Society, 2010, vol. 132, # 47, p. 16805 - 16811
[11] Patent: US2012/178913, 2012, A1, . Location in patent: Page/Page column 5
[12] Asian Journal of Chemistry, 2012, vol. 24, # 3, p. 1170 - 1174
[13] Asian Journal of Chemistry, 2012, vol. 24, # 3, p. 1237 - 1241
[14] Journal of Natural Products, 2013, vol. 76, # 7, p. 1388 - 1391
[15] Patent: CN103601742, 2016, B, . Location in patent: Paragraph 0102-0104
[16] Patent: CN105130871, 2018, B, . Location in patent: Paragraph 0038; 0042
10
[ 52-90-4 ]
[ 18598-63-5 ]
Reference:
[1] Chemical and Pharmaceutical Bulletin, 1981, vol. 29, # 6, p. 1554 - 1560
[2] Patent: US4745201, 1988, A,
11
[ 67-56-1 ]
[ 1447695-69-3 ]
[ 39994-75-7 ]
[ 6306-52-1 ]
[ 60667-85-8 ]
[ 18598-74-8 ]
[ 18598-63-5 ]
[ 2133-40-6 ]
Reference:
[1] Journal of Natural Products, 2013, vol. 76, # 7, p. 1388 - 1391
12
[ 18598-63-5 ]
[ 220168-39-8 ]
[ 3532-25-0 ]
[ 32854-09-4 ]
[ 65-85-0 ]
Reference:
[1] Australian Journal of Chemistry, 2011, vol. 64, # 4, p. 443 - 453
With thionyl chloride In methanol for 3h; Reflux; Inert atmosphere;
4.6.3. General method for preparation of 2-aryl-1,3-thiazolidinemethyl esters (11a-f)
General procedure: These compounds 11a-f were prepared using the generalmethod described by Gududuru et al. [35].Thionyl chloride (8.3 mL, 110 mmol) was added dropwise underan atmosphere of argon to a solution of L-cysteine (8) (9.00 g,74 mmol) in 150mL MeOH. The reaction mixture was refluxed for3 h then evaporated in vacuo, then co-evaporated with toluene(2 5 mL) to afford the hydrochloride salt of the methyl ester of Lcysteine(9) as white solid. One-sixth of this material (9)(12.4 mmol) was dissolved in water/ethanol (1:1) (15 mL). Sodiumhydrogen carbonate (1.14 g, 13.6 mmol) was added and, after10 min, the aromatic aldehyde (10a-f) (12.38 mmol) was added andthe reaction mixture was stirred for 14 h. The ethanol was evaporatedin vacuo and the aqueous residue was extracted with DCM(50 mL). The organic layer was washed with water (25 mL), driedover Na2SO4, filtered and evaporated in vacuo to afford the crudeproducts 11a-f.
96%
With acetyl chloride at 0℃; for 2h; Reflux;
General Procedure for the Synthesis of 2d-f and 2d'-f'
General procedure: Acetyl chloride (1.6 mL, 22 mmol) was added to MeOH (100 mL), and the solution was cooled to 0°C. The solution was stirred for 5 min. Amino acid (L-serine, D-serine, L-cysteine, D-cysteine, L-2,3-diaminopropionic acid, and D-2,3-diaminopropionic acid) (20 mmol) was then added to the acetyl chloride solution in methanol (MeOH), and the solution was heated to reflux for 2 h, then cooled to room temperature.The reaction was evaporated under reduced pressure and gavea colorless solid. The solid was washed with CH2Cl2 (20 mL)to give amino acid methyl ester hydrochloride (2d-f, 2d-f)as a white solid. The yields of 2d, d, e, e, f and f were 95%,96%, 94%, 96%, 95%, 95%, respectively.
94%
Stage #1: methanol With acetyl chloride at 0℃; for 0.0833333h; Inert atmosphere;
Stage #2: L-Cysteine at 20℃; for 36h; Inert atmosphere;
73%
With hydrogenchloride at 25℃; for 21h;
65%
at 25℃; for 24h;
38%
With thionyl chloride for 5h; Reflux;
Synthesis of methyl amino acids hydrochlorides[16]
General procedure: To a solution of thionyl chloride (2.18 mL, 0.03 mol) inmethanol (10 mL), the appropriate amino acid (0.01 mol)was added. The resulting solution was refluxed for 5 h. Afterthis time, the solution was cooled to room temperature, thesolvent was removed under reduced pressure and the residuewas recrystallized from ethyl acetate. Yield of obtainedproducts: methyl L-phenylalanine hydrochloride - 89%,methyl L-alanine hydrochloride - 65%, methyl L-valinehydrochloride - 90%, methyl L-leucine hydrochloride -91%, methyl L-cysteine hydrochloride - 38%, methyl L-tryptophanhydrochloride - 82%.
With hydrogenchloride for 12h;
With hydrogenchloride at 0 - 20℃; for 24h; Inert atmosphere;
With thionyl chloride at 20℃; for 24h;
Stage #1: methanol With acetyl chloride at 0℃; for 0.25h; Inert atmosphere;
Stage #2: L-Cysteine at 0 - 20℃; Inert atmosphere;
With acetyl chloride at 0 - 20℃; Inert atmosphere;
With acetyl chloride at 0 - 20℃; Inert atmosphere; Cooling with ice;
1 N-Boc-L-Cysteine methyl ester (BocCysOMe)
Example 1 N-Boc-L-Cysteine methyl ester (BocCysOMe) Anhydrous MeOH (100 mL) was added to a flame dried 250 mL round bottom flask equipped with a Teflon coated stir bar. The solvent was stirred and cooled to 0° C. and acetyl chloride (248 mmol, 17.6 mL) was added dropwise over 5 minutes. The solution was stirred an additional 10 minutes at 0° C. to give a concentrated solution of HCl. L-Cysteine (2.00 g, 16.51 mmol) was then added in one portion and the flask flushed briefly with argon. The ice bath was removed and the reaction was stirred at room temperature for 24 hours. The solvent was then removed under reduced pressure to give the crude cysteine methyl ester hydrochloride as a pale yellow solid.
With thionyl chloride at 60 - 70℃;
With thionyl chloride at 55℃; for 6h;
With hydrogenchloride at 100℃; for 0.5h;
With acetyl chloride for 3h;
13 Examble 13
Compound 16 (1.21g, 10mmol) dissolved in methanol (50 ml), dropwise acetyl chloride (2.1 ml, 30mmol), stirring 3h, decompression turns on lathe methanol, the residue is neutralized by saturated sodium bicarbonate solution, extracted with ethyl acetate organic phase (200mLx3), combined with the phase, the organic phase with saturated salt water washing, dry anhydrous sodium sulfate, concentrated to obtain compound 17 crude product (1.68g, 98%).
Stage #1: methanol With thionyl chloride at -11℃; for 1h;
Stage #2: L-Cysteine at -11 - 65℃; for 7h;
1.1 Step 1. Preparation of L-cysteine methyl ester hydrochloride:
0.12 mol of thionyl chloride was slowly added dropwise to 50 mL of anhydrous methanol at -11 ° C, and after stirring for 1 hour, 0.1 mol of L-cysteine was added, and the mixture was stirred at room temperature for 3 hours, and then stirred at 65 ° C for 4 hours. The reaction product was dissolved in a mixed solvent of ethyl acetate and petroleum ether (volume ratio 1:1) by rotary evaporation, and crystals were obtained at 0 ° C.
With thionyl chloride at 0 - 40℃; for 3h;
With thionyl chloride at 0 - 40℃; for 3h;
2.1. Synthesis of methyl ester hydrochloride: General Method A
General procedure: SOCl2 (1.5 eq) was added dropwise to stirring anhydrous MeOH (2 M) at 0 °C, followed by L-amino acid (1 eq) portion-wise. The mixture was heated to 40 °C and stirred at this temperature for 3 h. The solvent was then evaporated under reduced pressure to give methyl ester hydrochlorides 1a-d.
With thionyl chloride at 0 - 20℃; Schlenk technique;
With thionyl chloride at 0 - 40℃; for 3h;
Synthesis of Methyl Ester Hydrochloride: General Method A
General procedure: SOCl2 (1.5 eq) was added dropwise to stirring anhydrous MeOH (2M) at 0°C, followed by L-amino acid (1eq) portion-wise. The mixture was heated to 40°C and stirred at this temperature for 3 h. The solvent wasthen evaporated under reduced pressure to give methyl ester hydrogen chlorides.
Stage #1: L-Cysteine With chloro-trimethyl-silane at 20℃; for 0.333333h;
Stage #2: methanol at 20℃; for 24h;
Under ice-bath condition, 3 ml SOCl2 was added dropwise to 35 ml methanol in the presence of nitrogen atmosphere. Afterward, the solution was stirred at room temperature for 1 h, then 1 g Cys·HCl·H2O was added in batches to the solution. And the mixture solution reacted at room temperature for 3 h, and then refluxed for 1 h. Removing the volatile component and solvent, the residue was recrystallized with CH3OH-CH2Cl2, and 0.84 g white solid was obtained with 85.9% yield. IR (KBr, cm-1): 3040.4 (s, NH2), 1709.7 (s, C=O), 2580 (w, SH). 1H NMR (D2O, TMS, ppm); delta 4.453 (t, 1H, CH, J = 5.2 Hz), 3.871 (s, 3H, CH3), 3.164 (t, 2H, CH2, J = 6.4 Hz). Elemental Anal. Calcd for C4H10NO2SCl: C, 27.99; H, 5.87; N, 8.16%. Found: C, 28.11; H, 6.01; N, 8.08%.
With thionyl chloride; at 0 - 20℃; for 24h;
To a solution of L-cysteine hydrochloride (2 g, 12.6 mmol) in methanol (40 mL) at 0 C was dropped SOCl2 (1.5 mL, 7 mmol) and then the mixture was reacted at room temperature for 24 h. Methanol was evaporated to give 9 as a colorless oil which was directly used in the next process.
methyl (S)-2-methyl-3-thiazoline-4-carboxylate[ No CAS ]
methyl (R)-2-methyl-3-thiazoline-4-carboxylate[ No CAS ]
[ 6436-60-8 ]
Yield
Reaction Conditions
Operation in experiment
Stage #1: L-cysteine methyl ester hydrochloride; acetaldehyde With potassium acetate In methanol at 0℃; for 4h;
Stage #2: With manganese(IV) oxide In acetonitrile Title compound not separated from byproducts;
(S)-sodium 2,2-dimethyl-1,3-dioxolane-4-carboxylate[ No CAS ]
N-[(S)-2,3-dihydroxypropionyl]-L-cysteine methyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With 4-methyl-morpholine; In N-methyl-acetamide; methanol;
(a) To a solution of 60.0 g of sodium-[(S)-2,2-dimethyl-1,3-dioxolan-4-yl]carboxylate in 500 ml of dimethylformamide were added 136.0 g of O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium-hexafluorophosphate. The mixture was stirred at 20 C. for 0.5 hours, then 62 g L-cysteine methyl ester hydrochloride and subsequently 36.7 g of N-methylmorpholine were added. The mixture was stirred at 20 C. for 3.5 hours. The solvent was evaporated in vacuo and the oily residue was partitioned between water and ethyl acetate. The organic layer was washed successively with saturated sodium carbonate solution, saturated potassium hydrogensulfate solution, and brine, and then dried over magnesium sulfate. The solvent was evaporated in vacuo, and the residual oil was heated at reflux in a mixture of 50 ml cf trifluoroacetic acid and 500 ml of methanol for 2.5 hours. The solvent was evaporated in vacuo, and the residue was crystallized from tert-butyl-methyl-ether to give 33.4 g of N-[(S)-2,3-dihydroxypropionyl]-L-cysteine methyl ester as white crystals m.p. 90-92 C.
With triethylamine; In methanol; at 20℃; for 3h;Inert atmosphere;
General procedure: A 2-acylamidoacetonitrile was prepared similarly at room temperature, using an acid chloride as a starting compound. To a solution of the compound thus obtained (3 mmol) in dry methanol (50 mL) at room temperature under N2 atmosphere was added L-cysteine methyl ester hydrochloride (770 mg, 4.5 mmol) and triethylamine (0.63 mL, 4.5 mmol). The resulting mixture was stirred for 3 h and evaporated to dryness. The residue was taken up in CH2Cl2 and washed with saturated NaHCO3 solution and brine. The organic extract was dried over sodium sulfate, filtered, evaporated, and purified by column chromatography (silica gel, hexane/ethyl acetate, 5:1) to give a methyl ester of compounds 14 - 17. Precooled LiOH (0.9 mL, 1 N, 0.9 mmol) was added to the methyl ester (1.0 mmol) in methanol (5 mL) at 0 oC. The suspension was stirred for 1 h at room temperature, diluted with acetone (20 mL) to precipitate the product. The white powder was filtered and dried to give compounds 14 - 17.
methyl-2-(L-glucopentahydroxypentyl)thiazolidine-4(R)-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With pyridine at 60℃; for 1h;
With pyridine at 60℃; for 2h;
With pyridine at 60℃; for 2h;
General procedure: Compound 1 (2.0 mg) was dissolved in 1.0 N HCl (dioxane/H2O, 1:1, v/v, 1.0 mL) and then heated to 80 °C in a water bath for 3 h. The acidic solution was neutralized with silver carbonate and the solvent thoroughly driven out under N2 gas overnight. After extraction with ethyl acetate, the aqueous layer was concentrated to dryness using N2 gas. The residue was dissolved in 0.1 mL of dry pyridine, and then L-cysteine methyl ester hydrochloride in pyridine (0.06 M, 0.1 mL) was added to the solution. The reaction mixture was heated at 60 °C for 2 h, and 0.1 mL of trimethylsilylimidazole solution was added, followed by heating at 60 °C for 1.5 h. The dried product was partitioned with n-hexane and H2O (0.1 mL, each), and the organic layer was analyzed by gas liquid chromatography (GC): Column: column SPB-1 (0.25 mm x 30 m); detector FID, column temp 210 °C, injector temperature 270 °C, detector temperature 300 °C, carrier gas He. The absolute configuration of the monosaccharide was confirmed to be D-glucose by comparison of the retention time of the monosaccharide derivative (tR 14.11 min) with that of authentic sugar derivative samples prepared in the same manner D-glucose derivative tR 14.11 min, L-glucose derivative tR 14.26 min).
With pyridine at 60℃; for 2h;
Acid Hydrolysis and Derivatization
General procedure: Eachcompound (1.0 mg) was refluxed with 1 M HCl (3 mL) for2 h under constant stirring. The reaction was diluted with water and extractionwith EtOAc (3 ×5 mL).The aqueous layer was evaporated and cryo-desiccated. The residue was dissolved in dry pyridine (1 mL),and L-cysteinemethyl ester hydrochloride (3 mg) was added. The mixture was stirred at 60 for 2 h, 150 μL ofAc2O wasadded, and stirred at 90 for another 1 h. The reaction was evaporated to givemethyl 3-acetyl-2R-(1'R, 2'S, 3'R, 4'R,5-pentaacetoxypenta-1-yl)-thiazolidine-4R-carboxylatefor D-glucoseor methyl 3-acetyl-2R-(1'S, 2'R, 3'S, 4'S,5-pentaacetoxypenta-1-yl)-thiazolidine-4R-carboxylatefor L-glucose.
General procedure: Each compound (1 mg) was treated with 2 M HCl (10 ml) under conditions of reflux at 80 C this being maintained for 4 h. Each reaction mixture was concentrated to dryness, partitioned between CHCl3 and H2O and then the H2O layer was concentrated to dryness to yield a mixture of sugars. Each mixture was dissolved in anhydrous pyridine (1 ml) and reacted with l-cysteine methyl ester hydrochloride (1 mg) in an oven at 60 C for 2 h. After the reaction mixture was evaporated under a stream of N2, trimethylsilyl imidazole (0.2 ml) was added, and the mixture warmed to 60 C for another 1 h. After drying the solution, the products were partitioned between cyclohexane and H2O. The same reactions were applied to standard sugars. Then the cyclohexane layers were analyzed by gas chromatography on a column, AT-SE-30 (0.5 mum × 0.32 mm × 30 m); column temperature, 250 C; detector temperature, 250 C; injection temperature, 230 C; carrier gas, N2. The derivatives of d-glucose, l-glucose, l-rhamnose, d-apiose, l-arabinose and d-xylose gave peaks at tR 25.67, 26.81, 16.33, 12.69, 13.09 and 12.94 min, respectively.
methyl-2-(D-glucopentahydroxypentyl)thiazolidine-4(R)-carboxylate[ No CAS ]
C10H19NO6S[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
General procedure: Each compound (1 mg) was treated with 2 M HCl (10 ml) under conditions of reflux at 80 C this being maintained for 4 h. Each reaction mixture was concentrated to dryness, partitioned between CHCl3 and H2O and then the H2O layer was concentrated to dryness to yield a mixture of sugars. Each mixture was dissolved in anhydrous pyridine (1 ml) and reacted with l-cysteine methyl ester hydrochloride (1 mg) in an oven at 60 C for 2 h. After the reaction mixture was evaporated under a stream of N2, trimethylsilyl imidazole (0.2 ml) was added, and the mixture warmed to 60 C for another 1 h. After drying the solution, the products were partitioned between cyclohexane and H2O. The same reactions were applied to standard sugars. Then the cyclohexane layers were analyzed by gas chromatography on a column, AT-SE-30 (0.5 mum × 0.32 mm × 30 m); column temperature, 250 C; detector temperature, 250 C; injection temperature, 230 C; carrier gas, N2. The derivatives of d-glucose, l-glucose, l-rhamnose, d-apiose, l-arabinose and d-xylose gave peaks at tR 25.67, 26.81, 16.33, 12.69, 13.09 and 12.94 min, respectively.
Stage #1: N-acetyldopamine With formic acid; sodium sulfate; silver(l) oxide In methanol at 20℃; for 0.25h; Darkness;
Stage #2: L-cysteine methyl ester hydrochloride In methanol
Methyl 6-(2-acetylaminoethyl)-4-hydroxy-benzothiazole-2-carboxylate
General procedure: Silver(I) oxide (256 mg, 1.1 mmol) and sodium sulfate (251 mg, 1.8 mmol) were added to asolution of N-acetyldopamine 8 (60 mg, 0.3 mmol) and formic acid (42 μL, 1.1 mmol) inmethanol (4 mL) and the black suspension was stirred for 15 min in the dark at rt then filteredthrough a pad of Celite. The filter cake was washed with methanol (2 × 6 mL) and thecombined red filtrates were immediately added dropwise to a solution of cysteine methylester hydrochloride (57 mg, 0.3 mmol) in methanol (2 mL). After addition had completed thepale green solution was concentrated to give the cysteine adduct as a pale yellow/green foamthat was used directly without purification; (Found: [M+H+], 329.1160. C14H21N2O5S+requires 329.1166.); The above foam was dissolved in water (0.7mL) and a solution ofiron(III) chloride hexahydrate (442 mg, 1.6 mmol) in water (1.8 mL) was slowly addeddropwise with vigorous stirring. The mixture was stirred for 72 h at rt, then diluted with water(10 ml) and extracted with ethyl acetate (3 × 10 mL). The combined organic extracts werewashed with water (30 mL) and brine (30 mL), dried (Na2SO4) and concentrated. The residuewas subjected to flash column chromatography on silica gel, eluting with ethanol-ethylacetate (1:9) to give the title compound as yellow solid
With triethylamine; In ethanol; water; for 0.333333h;
ACSO synthesis was performed as previously describedwith some modifications [13,14]. l-Cysteine methyl esterhydrochloride (3.0 g, 5.83 mmol) was dissolved in ethanol/H2O (2:1, v/v, 30 mL), before triethylamine (7.2 mL,17.2 mmol) and allyl bromide (2.9 mL, 10.4 mmol) wereadded. After stirring for 20 min, the reaction mixturewas then filtered and concentrated in vacuo to yieldS-allyl-L-cysteine (white crystals). S-allyl-L-cysteine wasdissolved in water and the 30% w/w hydrogen peroxide(weight of S-allyl-L-cysteine (g) × 1.26 mL) was added.After stirring overnight at room temperature, the solutionwas filtered in vacuo. Then, the filtrate was mixedwith 1% acetate (5 mL) and 99.5% ethanol (75 mL) at160 C. The reaction mixture was cooled to 4 C andstirred for 60 min and then all solvents and reagentswere removed in vacuo. Without further procedures,the ACSO (white crystals) obtained should have been of sufficient purity for use in animal experiments andthis was confirmed from NMR spectra recorded on anECA500 spectrometer (JEOL, Tokyo, Japan).
General procedure: A solution of a compound (2.0 mg) in HCl 1.0M (3.0 mL) was heated under reflux for 2h. Then, the reaction mixture was concentrated in vacuum to dryness. The residue was extracted with CHCl3 and H2O (5 mL each, 3 times). Next, the sugar residue obtained by concentration of the water layer was dissolved in dry pyridine (0.1mL). Then L-cysteine methyl ester hydrochloride in pyridine (0.06 M, 0.1 mL) was added to the solution. After heating the reaction mixture at 60C for 2h, 0.1 mL of trimethylsilylimidazole was added. Heating at 60C was continued for a further 2h, and the mixture was evaporated in vacuum to give a dried product, which was partitioned between n-hexane and H2O. The n-hexane layer was analyzed using the GC procedure (General Procedures). The peaks of the hydrolysates of the respective glycosides were detected at tR 8.21 min (D-<strong>[609-06-3]xylose</strong>) for 1 and at tR 4.50 min (L-arabinose) for 2. The retention times for the authentic samples (Sigma) after being treated similarly were 8.21 min (D-<strong>[609-06-3]xylose</strong>), 8.66 min (<strong>[609-06-3]L-<strong>[609-06-3]xylose</strong></strong>), and 4.50 min (L-arabinose), respectively. Co-injection of the hydrolysates of the compounds with standard D-<strong>[609-06-3]xylose</strong> in 1 and L-arabinose in 2 gave single peaks.
methyl 2-(cyclopropylmethyl)Δ2-1 ,3-thiazoline-4-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Stage #1: 2-cyclopropylacetonitrile With acetyl chloride In ethanol at 0 - 20℃;
Stage #2: L-cysteine methyl ester hydrochloride With triethylamine In dichloromethane at 0 - 20℃;
1
Cyclopropylacetonitrile was reacted with ethanol and acetyl chloride to generate 2-cyclopropyl-1-ethoxy-1-ethanimine that was reacted with R)-cysteine methyl esterhydrochloride and Et3N in CH2CI2 without any workup to form Methyl 2-(cyclopropyl methyl)2-1 ,3-thiazoline-4-carboxylate. (1 -Naphthyl)acetic acid activated with DCC and DMAP was reacted with 2,2-Dimethyl-1 ,3-dioxane-4,6-dione in DCM to give 5- [1 -Hydroxy-2-(1 -naphthyl)ethylidene]-2,2-dimethyl-1 ,3-dioxane-4,6-dione.These two building blocks were allowed to react with TFA at elevated temperature to give Benzyl (3R)-7-cyclopropyl-4-oxo-6-[m-(trifluoromethyl)phenyl]methyl}-1 -thia-3a-aza-3-indancarboxylate. Hydrolysis with LiOH in THF or LiBr and Et3N in wet (2%)aceton itrile gave (3R)-7-Cyclopropyl-6-[(1 -naphthyl )methyl]-4-oxo-1 -thia-3a-aza-3- indancarboxylic acid (Scheme 1). NMR and MS data are provided in Table 1.