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【结 构 式】 
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【分子编号】33059 【品名】(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[[(2R,3R)-2-([[(2S)-3-methyl-2-([[(4-nitrobenzyl)oxy]carbonyl]amino)butanoyl]amino]methyl)tetrahydro-3-furanyl]sulfanyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid 【CA登记号】 |
【 分 子 式 】C28H36N4O10S 【 分 子 量 】620.6808 【元素组成】C 54.18% H 5.85% N 9.03% O 25.78% S 5.17% |
合成路线1
该中间体在本合成路线中的序号：(XXVII)Coupling of carbapenem phosphate (VIII) with thiol (XIII) using diisopropylethylamine gave rise to sulfide (XIX). Hydrogenolysis of the p-nitrobenzyl group of (XIX) with simultaneous azide reduction in the presence of Pd/C provided (XX). Treatment of p-nitrobenzyl chloroformate (XXI) with p-nitrophenol (XXII) afforded the nitrophenyl carbonate (XXIII), which was coupled with L-valine (XXIV), yielding carbamate (XXV). Activation of (XXV) with N-hydroxy succinimide and DCC then produced the succinimidyl ester (XXVI). Amine (XX) was coupled with succinimidyl ester (XXVI) to furnish amide (XXVII). The p-nitrobenzyl ester was finally removed by hydrogenation over Pd/C to provide the title compound.
| 【1】 Lin, Y.-I.; et al.; Peptidic prodrugs of novel aminomethyl-THF 1beta-methylcarbapenems. Bioorg Med Chem Lett 1997, 7, 13, 1665. |
| 【2】 Lin, Y.-I.; Bitha, P.; Sakya, S.; Strohmeyer, T.W.; Bush, K. (American Cyanamid Co.); Novel 2-thiosubstd. carbapenems. CA 2118961; EP 0617036; JP 1994321948; US 5602118 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 13224 | 4-nitrobenzyl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | 90776-59-3 | C29H27N2O10P | 详情 | 详情 |
| (XIII) | 33047 | (2R,3R)-2-(azidomethyl)tetrahydro-3-furanthiol; (2R,3R)-2-(azidomethyl)tetrahydro-3-furanylhydrosulfide | C5H9N3OS | 详情 | 详情 | |
| (XIX) | 33053 | 4-nitrobenzyl (4R,5S,6S)-3-[[(2R,3R)-2-(azidomethyl)tetrahydro-3-furanyl]sulfanyl]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C22H25N5O7S | 详情 | 详情 | |
| (XX) | 33054 | (4R,5S,6S)-3-[[(2R,3R)-2-(aminomethyl)tetrahydro-3-furanyl]sulfanyl]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid | C15H22N2O5S | 详情 | 详情 | |
| (XXI) | 33055 | 1-[[(chlorocarbonyl)oxy]methyl]-4-nitrobenzene | 4457-32-3 | C8H6ClNO4 | 详情 | 详情 |
| (XXII) | 11236 | 4-Nitrophenol; p-Nitrophenol | 100-02-7 | C6H5NO3 | 详情 | 详情 |
| (XXIII) | 33056 | 4-nitrobenzyl 4-nitrophenyl carbonate | C14H10N2O7 | 详情 | 详情 | |
| (XXIV) | 21056 | (R)-(-)-Valine; D-Valine; (R)-alpha-Aminoisovaleric acid | 640-68-6 | C5H11NO2 | 详情 | 详情 |
| (XXV) | 33057 | (2S)-3-methyl-2-([[(4-nitrobenzyl)oxy]carbonyl]amino)butyric acid | C13H16N2O6 | 详情 | 详情 | |
| (XXVI) | 33058 | 4-nitrobenzyl (1S)-1-[[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl]-2-methylpropylcarbamate | C17H19N3O8 | 详情 | 详情 | |
| (XXVII) | 33059 | (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[[(2R,3R)-2-([[(2S)-3-methyl-2-([[(4-nitrobenzyl)oxy]carbonyl]amino)butanoyl]amino]methyl)tetrahydro-3-furanyl]sulfanyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid | C28H36N4O10S | 详情 | 详情 |