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【结 构 式】 
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【分子编号】16095 【品名】tert-butyl (2S,4R)-2-(hydroxymethyl)-4-[(methylsulfonyl)oxy]tetrahydro-1H-pyrrole-1-carboxylate 【CA登记号】 |
【 分 子 式 】C11H21NO6S 【 分 子 量 】295.35688 【元素组成】C 44.73% H 7.17% N 4.74% O 32.5% S 10.86% |
合成路线1
该中间体在本合成路线中的序号：(III)A new synthesis of S-4661 has been reported: The protection of trans-4-hydroxy-L-proline with tert-butoxycarbonyl anhydride gives N-(tert-butoxycarbonyl)-4(R)-hydroxy-L-proline (II), which is successively treated with ethyl chloroformate, mesylated with mesyl chloride and reduced with NaBH4 yielding (2S,4R)-1-(tert-butoxycarbonyl)-2-(hydroxymethyl)-4-(methanesulfonyloxy)pyrrolidine (III). The reaction of (III) with potassium thioacetate affords Compound (IV), which is condensed with N-(tert-butoxycarbonyl)sulfamide (V) by means of diethyl azodicarboxylate and triphenylphosphine to give the protected pyrrolidinesulfamide (VI). The deacetylation of (VI) with sodium methoxide yields (2S,4S)-1-(tert-butoxycarbonyl)-2-[N-(tert-butoxycarbonyl)-N-sulfamoylaminomethyl]-4-sulfanylpyrrolidine (VII), which is then condensed with (1R,5S,6S)-2-(diphenoxyphosphoryloxy)-6-[1(R)-hydroxyethyl]-1-methyl-1-carba-2-penem-3-carboxylic acid diphenylmethyl ester (VIII) by means of diisopropylethylamine to afford the protected final product (IX). Finally, this compound is deprotected with AlCl3 in anisole.
| 【1】 Motokawa, K.; Nishitani, Y.; Iso, Y.; Kii, M.; Irie, T.; Sendo, Y.; Iwaki, T.; Synthesis and modification of a novel 1beta-methyl carbapenem antibiotic, S-4661. J Antibiot 1996, 49, 5, 478. |
| 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) | 14489 | (2S,4R)-4-hydroxytetrahydro-1H-pyrrole-2-carboxylic acid; L-Hydroxyproline | 51-35-4 | C5H9NO3 | 详情 | 详情 |
| (II) | 16094 | (2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid;1-(tert-butoxycarbonyl)-4®-hydroxy-L-proline;(2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxytetrahydro-1H-pyrrole-2-carboxylic acid | 16094 | C10H17NO5 | 详情 | 详情 |
| (III) | 16095 | tert-butyl (2S,4R)-2-(hydroxymethyl)-4-[(methylsulfonyl)oxy]tetrahydro-1H-pyrrole-1-carboxylate | C11H21NO6S | 详情 | 详情 | |
| (IV) | 16096 | tert-butyl (2S,4S)-4-(acetylsulfanyl)-2-(hydroxymethyl)tetrahydro-1H-pyrrole-1-carboxylate | C12H21NO4S | 详情 | 详情 | |
| (V) | 16097 | tert-butyl 2,2-dioxo-2lambda(6)-diazathiane-1-carboxylate | 148017-28-1 | C5H12N2O4S | 详情 | 详情 |
| (VI) | 16098 | tert-butyl (2S,4S)-4-(acetylsulfanyl)-2-[[(aminosulfonyl)(tert-butoxycarbonyl)amino]methyl]tetrahydro-1H-pyrrole-1-carboxylate | C17H31N3O7S2 | 详情 | 详情 | |
| (VII) | 16099 | tert-butyl (2S,4S)-2-[[(aminosulfonyl)(tert-butoxycarbonyl)amino]methyl]-4-sulfanyltetrahydro-1H-pyrrole-1-carboxylate | C15H29N3O6S2 | 详情 | 详情 | |
| (VIII) | 16100 | benzhydryl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C35H32NO8P | 详情 | 详情 | |
| (IX) | 16101 | benzhydryl (4R,5S,6S)-3-[[(3S,5S)-5-[[(aminosulfonyl)(tert-butoxycarbonyl)amino]methyl]-1-(tert-butoxycarbonyl)pyrrolidinyl]sulfanyl]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C38H50N4O10S2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)
| 【1】 Zhang AY, Zhu XY, Yuan ZD.2006.Synthesis of doripenem. Chin J Pharmaceuticals, 37: 361～363 |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 67084 | (4S)-1-tert-butyl 2-methyl 4-((methylsulfonyl)oxy)pyrrolidine-1,2-dicarboxylate | C12H21NO7S | 详情 | 详情 | |
| (I) | 67082 | (4S)-4-hydroxypyrrolidine-2-carboxylic acid | C5H9NO3 | 详情 | 详情 | |
| (II) | 67083 | (4S)-methyl 4-hydroxypyrrolidine-2-carboxylate hydrochloride | C6H11NO3.HCl | 详情 | 详情 | |
| (IV) | 16095 | tert-butyl (2S,4R)-2-(hydroxymethyl)-4-[(methylsulfonyl)oxy]tetrahydro-1H-pyrrole-1-carboxylate | C11H21NO6S | 详情 | 详情 | |
| (V) | 16096 | tert-butyl (2S,4S)-4-(acetylsulfanyl)-2-(hydroxymethyl)tetrahydro-1H-pyrrole-1-carboxylate | C12H21NO4S | 详情 | 详情 | |
| (VI) | 16098 | tert-butyl (2S,4S)-4-(acetylsulfanyl)-2-[[(aminosulfonyl)(tert-butoxycarbonyl)amino]methyl]tetrahydro-1H-pyrrole-1-carboxylate | C17H31N3O7S2 | 详情 | 详情 | |
| (VII) | 16099 | tert-butyl (2S,4S)-2-[[(aminosulfonyl)(tert-butoxycarbonyl)amino]methyl]-4-sulfanyltetrahydro-1H-pyrrole-1-carboxylate | C15H29N3O6S2 | 详情 | 详情 | |
| (VIII) | 16100 | benzhydryl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C35H32NO8P | 详情 | 详情 | |
| (IX) | 16101 | benzhydryl (4R,5S,6S)-3-[[(3S,5S)-5-[[(aminosulfonyl)(tert-butoxycarbonyl)amino]methyl]-1-(tert-butoxycarbonyl)pyrrolidinyl]sulfanyl]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C38H50N4O10S2 | 详情 | 详情 | |
| (X) | 67085 | 4-nitrobenzyl 6-(1-hydroxyethyl)-4-methyl-7-oxo-3-((5-((sulfamoylamino)methyl)pyrrolidin-3-yl)thio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C22H29N5O8S2 | 详情 | 详情 |