【结 构 式】 |
【分子编号】16083 【品名】4-methoxybenzyl (2S,4S)-2-(hydroxymethyl)-4-(tritylsulfanyl)-1-pyrrolidinecarboxylate 【CA登记号】 |
【 分 子 式 】C33H33NO4S 【 分 子 量 】539.69536 【元素组成】C 73.44% H 6.16% N 2.6% O 11.86% S 5.94% |
合成路线1
该中间体在本合成路线中的序号:(VI)A new synthesis of S-4661 has been reported: The esterification of trans-4-hydroxy-L-proline (I) with methanol/HCl gives the corresponding methyl ester (II), which is N-protected as trans-N-(4-methoxybenzyloxycarbonyl)-4-hydroxy-L-proline methyl ester (III). The mesylation of (III) with methanesulfonyl chloride and triethylamine in dichloromethane affords the 4-O-mesylate (IV), which is treated with sodium triphenylmethylsulfide giving cis-N-(4-methoxybenzyloxycarbonyl)-4-(triphenylmethylsulfanyl)-L-prolin e methyl ester (V). The reduction of (V) with LiBH4 in THF yields the corresponding methanol (VI), which is mesylated as before affording (VII). The reaction of (VII) with potassium phthalimide (VIII) gives the adduct (IX), which is cleaved with hydrazine yielding (2S,4S)-2-(aminomethyl)-1-(4-methoxybenzyloxycarbonyl)-4-(triphenylmeth ylsulfanyl)pyrrolidine (X). The condensation of (X) with N-(4-methoxybenzyl)sulfamoyl chloride (XI) by means of triethylamine affords the corresponding protected sulfamide (XII). Deprotection of the trityl group of (XII) by treatment with silver nitrate and pyridine affords compound (XIII) with a free SH group. The reaction of (XIII) with (1R,5S,6S)-2-(diphenoxyphosphoryloxy)-6-[1(R)-hydroxyethyl]-1-methyl-1-carba-2-penem-3-carboxylic acid 4-methoxybenzyl ester (XIV) by means of diisopropylethylamine yields the protected final product (XV), which is finally treated with AlCl3 in anisole to eliminate the protecting groups.
【1】 Iso, Y.; Motokawa, K.; Nishitani, Y.; Nishino, Y.; Irie, T.; A novel 1beta-methylcarbapenem antibiotic, S-4661. Synthesis and structure-activity relationships of 2-(5-substituted pyrrolidin-3-ylthio)-1beta-methylcarbapenems. J Antibiot 1996, 49, 2, 199. |
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) | 15796 | methyl (2S,4R)-4-hydroxytetrahydro-1H-pyrrole-2-carboxylate | C6H11NO3 | 详情 | 详情 | |
(III) | 16080 | 1-(4-methoxybenzyl) 2-methyl (2S,4R)-4-hydroxytetrahydro-1H-pyrrole-1,2-dicarboxylate | C15H19NO6 | 详情 | 详情 | |
(IV) | 16081 | 1-(4-methoxybenzyl) 2-methyl (2S,4R)-4-[(methylsulfonyl)oxy]tetrahydro-1H-pyrrole-1,2-dicarboxylate | C16H21NO8S | 详情 | 详情 | |
(V) | 16082 | 1-(4-methoxybenzyl) 2-methyl (2S,4S)-4-(tritylsulfanyl)-1,2-pyrrolidinedicarboxylate | C34H33NO5S | 详情 | 详情 | |
(VI) | 16083 | 4-methoxybenzyl (2S,4S)-2-(hydroxymethyl)-4-(tritylsulfanyl)-1-pyrrolidinecarboxylate | C33H33NO4S | 详情 | 详情 | |
(VII) | 16084 | 4-methoxybenzyl (2S,4S)-2-[[(methylsulfonyl)oxy]methyl]-4-(tritylsulfanyl)-1-pyrrolidinecarboxylate | C34H35NO6S2 | 详情 | 详情 | |
(VIII) | 10926 | (1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)potassium | C8H4KNO2 | 详情 | 详情 | |
(IX) | 16086 | 4-methoxybenzyl (2S,4S)-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-4-(tritylsulfanyl)-1-pyrrolidinecarboxylate | C41H36N2O5S | 详情 | 详情 | |
(X) | 16087 | 4-methoxybenzyl (2S,4S)-2-(aminomethyl)-4-(tritylsulfanyl)-1-pyrrolidinecarboxylate | C33H34N2O3S | 详情 | 详情 | |
(XI) | 16088 | chloro([[(4-methoxybenzyl)oxy]carbonyl]amino)dioxo-lambda(6)-sulfane | C9H10ClNO5S | 详情 | 详情 | |
(XII) | 16089 | 4-methoxybenzyl (2S,4S)-2-([[([[(4-methoxybenzyl)oxy]carbonyl]amino)sulfonyl]amino]methyl)-4-(tritylsulfanyl)-1-pyrrolidinecarboxylate | C42H43N3O8S2 | 详情 | 详情 | |
(XIII) | 16090 | 4-methoxybenzyl (2S,4S)-2-([[([[(4-methoxybenzyl)oxy]carbonyl]amino)sulfonyl]amino]methyl)-4-sulfanyl-1-pyrrolidinecarboxylate | C23H29N3O8S2 | 详情 | 详情 | |
(XIV) | 16075 | 4-methoxybenzyl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C30H30NO9P | 详情 | 详情 | |
(XV) | 16092 | 4-methoxybenzyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-3-[[(3S,5S)-1-[[(4-methoxybenzyl)oxy]carbonyl]-5-([[([[(4-methoxybenzyl)oxy]carbonyl]amino)sulfonyl]amino]methyl)pyrrolidinyl]sulfanyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C41H48N4O13S2 | 详情 | 详情 |