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【结 构 式】 
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【分子编号】29144 【品名】(2R,3S,4R,5R)-2-(aminocarbothioyl)-4-(benzoyloxy)-5-[(benzoyloxy)methyl]tetrahydro-3-furanyl benzoate 【CA登记号】 |
【 分 子 式 】C27H23NO7S 【 分 子 量 】505.54816 【元素组成】C 64.15% H 4.59% N 2.77% O 22.15% S 6.34% |
合成路线1
该中间体在本合成路线中的序号：(III)A new synthesis of thiazofurin has been described: The reaction of 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose (I) with trimethylsilyl cyanide and SnCl4 in dichloromethane gives 2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl cyanide (II), which is treated with H2S gas and dimethylaminopyridine (DMAP) in ethanol yielding the corresponding thioamide (III). The carefully controlled cyclization of (III) with 3-bromopyruvic acid ethyl ester (IV) by means of NaHCO3 in dimethoxyethane, followed by treatment with trifluoroacetic anhydride and 2,6-lutidine in the same solvent affords 2-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)thiazole-4-carboxylic acid ethyl ester (V). Elimination of the benzoyl protecting groups of (V) with NaOEt in ethanol gives 2-(beta-D-ribofuranosyl)thiazole-4-carboxylic acid ethyl ester (VI). Which is finally treated with dry ammonia in methanol to afford the target amide.
| 【1】 Garcia-Munoz, G.; Stud, M.; Fuertes, M.; Synthesis of C-glycocyl thiazoles. J Org Chem 1976, 41, 4074. |
| 【2】 Ramasamy, K.S.; Averett, D.; A modified synthesis of tiazofurin. Nucleosides Nucleotides 1999, 18, 11-12, 2425. |
| 【3】 Eastland, G.; Tiazofurine. Drugs Fut 1985, 10, 4, 304. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 26984 | (2R,3R,4R,5S)-5-(acetoxy)-4-(benzoyloxy)-2-[(benzoyloxy)methyl]tetrahydro-3-furanyl benzoate | C28H24O9 | 详情 | 详情 | |
| (II) | 29143 | (2S,3S,4R,5R)-4-(benzoyloxy)-5-[(benzoyloxy)methyl]-2-cyanotetrahydro-3-furanyl benzoate | C27H21NO7 | 详情 | 详情 | |
| (III) | 29144 | (2R,3S,4R,5R)-2-(aminocarbothioyl)-4-(benzoyloxy)-5-[(benzoyloxy)methyl]tetrahydro-3-furanyl benzoate | C27H23NO7S | 详情 | 详情 | |
| (IV) | 25183 | ethyl 3-bromo-2-oxopropanoate;ethyl 3-bromopyruvate;Bromopyruvic acid ethyl ester;ethyl 3-bromopyruvate;ethyl bromopyruvate | 70-23-5 | C5H7BrO3 | 详情 | 详情 |
| (V) | 29145 | ethyl 2-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1,3-thiazole-4-carboxylate | C11H15NO6S | 详情 | 详情 | |
| (VI) | 34062 | ethyl 2-[(2R,3S,4R,5R)-3,4-bis(benzoyloxy)-5-[(benzoyloxy)methyl]tetrahydro-2-furanyl]-1,3-thiazole-4-carboxylate | C32H27NO9S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)Reaction of 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose (I) with trimethylsilyl cyanide in the presence of boron trifluoride gave nitrile (II), which was treated with liquid hydrogen sulfide and DMAP to yield thioamide (III). Condensation of this thioamide with bromoketone (IV) in acetonitrile afforded the thiazole derivative (V). Hydrolysis of the benzoate esters of (V) using sodium methoxide in methanol, followed by protection of the resulting 2,3-diol with acetone and triethyl orthoformate produced the corresponding isopropylidene ketal (VI). Treatment of the primary alcohol group of (VI) with sulfamoyl chloride gave rise to the sulfamate ester (VII). Further condensation of (VII) with N-Boc-L-leucine furnished (IX). The Boc and isopropylidene groups of (IX) were finally eliminated with trifluoroacetic acid to provide the title compound.
| 【1】 Wang, W.; Gallant, P.; Hill, J.M.; Yu, G.; Wendler, P.; Kluge, A.F.; Yu, X.Y.; Synthesis and structure-activity relationships of a series of novel thiazoles as inhibitors of aminoacyl-tRNA synthetases. Bioorg Med Chem Lett 1999, 9, 3, 375. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 20984 | methyl (Z)-7-[(1R,2S,3R,5S)-5-(acetoxy)-2-[(E)-3-oxo-3-(4-propylcyclohexyl)-1-propenyl]-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]-5-heptenoate | C33H52O7 | 详情 | 详情 | |
| (II) | 29143 | (2S,3S,4R,5R)-4-(benzoyloxy)-5-[(benzoyloxy)methyl]-2-cyanotetrahydro-3-furanyl benzoate | C27H21NO7 | 详情 | 详情 | |
| (III) | 29144 | (2R,3S,4R,5R)-2-(aminocarbothioyl)-4-(benzoyloxy)-5-[(benzoyloxy)methyl]tetrahydro-3-furanyl benzoate | C27H23NO7S | 详情 | 详情 | |
| (IV) | 29211 | 1-bromo-4-phenyl-2-butanone | C10H11BrO | 详情 | 详情 | |
| (V) | 29212 | [(2R,3R,4S,5R)-3,4-bis(benzoyloxy)-5-(4-phenethyl-1,3-thiazol-2-yl)tetrahydro-2-furanyl]methyl benzoate | C37H31NO7S | 详情 | 详情 | |
| (VI) | 29213 | [(3aR,4R,6R,6aS)-2,2-dimethyl-6-(4-phenethyl-1,3-thiazol-2-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methanol | C19H23NO4S | 详情 | 详情 | |
| (VII) | 29214 | [(3aR,4R,6R,6aS)-2,2-dimethyl-6-(4-phenethyl-1,3-thiazol-2-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methylsulfamate | C19H24N2O6S2 | 详情 | 详情 | |
| (VIII) | 23663 | (2S)-2-[(tert-butoxycarbonyl)amino]-4-methylpentanoic acid；N-Boc-L-leucine | C11H21NO4 | 详情 | 详情 | |
| (IX) | 29215 | tert-butyl (1S)-1-[[([[(3aR,4R,6R,6aS)-2,2-dimethyl-6-(4-phenethyl-1,3-thiazol-2-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methoxy]sulfonyl)amino]carbonyl]-3-methylbutylcarbamate | C30H43N3O9S2 | 详情 | 详情 |