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【结 构 式】 
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【分子编号】48244 【品名】allyl (4R,5S,6S)-3-([(3S,5R)-1-[(allyloxy)carbonyl]-5-[4-((1S)-1-[[(allyloxy)carbonyl]amino]-3-amino-3-oxopropyl)phenyl]pyrrolidinyl]sulfanyl)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate 【CA登记号】 |
【 分 子 式 】C34H42N4O9S 【 分 子 量 】682.79504 【元素组成】C 59.81% H 6.2% N 8.21% O 21.09% S 4.7% |
合成路线1
该中间体在本合成路线中的序号：(XXV)Reaction of the carboxylic acid (XVI) with MsCl and TEA in THF yields the fully protected mixed anhydride (XVII). The chemo-selective ammonolysis of anhydride (XVII) gives amide (XVIII), which by displacement of the mesyloxy group with potassium thioacetate in hot DMF yields the thioacetate (XIX). Removal of the Boc protecting groups of (XIX) with HCl in ethyl acetate affords compound (XX), which is reprotected with allyl chloroformate (XXI) and TEA in dichloromethane to provide the bis(allyloxycarbonyl) compound (XXII). Hydrolysis of the thioacetate group of (XXII) with NaOH in methanol gives the thiol compound (XXIII), which is condensed with the carbape- nem diphenyl phosphate (XXIV) by means of DIEA in acetonitrile to provide the expected adduct (XXV). Finally, this compound is deprotected by a treatment with Bu3SnH and PdCl2(PPh3)2 in dichloromethane/water.
| 【1】 Yamada, K.; Miura, K.; Nishimura, I.; Shimizu, A.; Morishima, H.; Abe, S.; Nakajima, S.; Sakuraba, S.; Imamura, H.; Sato, H.; Sugimoto, Y.; Stereoselective synthesis of a broad spectrum 1 beta-methylcarbapenem, J-114,870. Tetrahedron 2000, 56, 39, 7705. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIV) | 32617 | allyl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C25H26NO8P | 详情 | 详情 | |
| (XVI) | 48235 | (3S)-3-[(tert-butoxycarbonyl)amino]-3-[4-[(2R,4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidinyl]phenyl]propionic acid | C23H34N2O7 | 详情 | 详情 | |
| (XVII) | 48238 | tert-butyl (2R,4R)-2-(4-[(1S)-1-[(tert-butoxycarbonyl)amino]-3-[(methylsulfonyl)oxy]-3-oxopropyl]phenyl)-4-[(methylsulfonyl)oxy]-1-pyrrolidinecarboxylate | C25H38N2O11S2 | 详情 | 详情 | |
| (XVIII) | 48239 | tert-butyl (2R,4R)-2-(4-[(1S)-3-amino-1-[(tert-butoxycarbonyl)amino]-3-oxopropyl]phenyl)-4-[(methylsulfonyl)oxy]-1-pyrrolidinecarboxylate | C24H37N3O8S | 详情 | 详情 | |
| (XIX) | 48240 | tert-butyl (2R,4S)-4-(acetylsulfanyl)-2-(4-[(1S)-3-amino-1-[(tert-butoxycarbonyl)amino]-3-oxopropyl]phenyl)-1-pyrrolidinecarboxylate | C25H37N3O6S | 详情 | 详情 | |
| (XX) | 48241 | S-((3S,5R)-5-[4-[(1S)-1,3-diamino-3-oxopropyl]phenyl]pyrrolidinyl) ethanethioate | C15H21N3O2S | 详情 | 详情 | |
| (XXI) | 38115 | 3-[(chlorocarbonyl)oxy]-1-propene | 2937-50-0 | C4H5ClO2 | 详情 | 详情 |
| (XXII) | 48242 | allyl (2R,4S)-4-(acetylsulfanyl)-2-[4-((1S)-1-[[(allyloxy)carbonyl]amino]-3-amino-3-oxopropyl)phenyl]-1-pyrrolidinecarboxylate | C23H29N3O6S | 详情 | 详情 | |
| (XXIII) | 48243 | C21H27N3O5S | 详情 | 详情 | ||
| (XXV) | 48244 | allyl (4R,5S,6S)-3-([(3S,5R)-1-[(allyloxy)carbonyl]-5-[4-((1S)-1-[[(allyloxy)carbonyl]amino]-3-amino-3-oxopropyl)phenyl]pyrrolidinyl]sulfanyl)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C34H42N4O9S | 详情 | 详情 |