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【结 构 式】 
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【分子编号】20044 【品名】S-phenyl (2R,3S)-2-ethyl-3-[[(1S)-1-phenylethyl]amino]-5-(trimethylsilyl)-4-pentynethioate 【CA登记号】 |
【 分 子 式 】C24H31NOSSi 【 分 子 量 】409.66778 【元素组成】C 70.37% H 7.63% N 3.42% O 3.91% S 7.83% Si 6.86% |
合成路线1
该中间体在本合成路线中的序号：(XXIV)4) The reaction of phenyl thiobutyrate (XIX) with 9-borabicyclo[3.3.1]nonane (9-BBN) gives the enol ester (XX), which is condensed with the optically active imine (XXI) [prepared from 3-(trimethylsilyl)propynal (XXIII) and (S)-alpha-methylbenzylamine (XXII)] to afford the adduct (XXIV). The cyclization of (XXIV) by means of tert-butylmagnesium chloride in ether yields 3alpha-ethyl-1-(alpha-methylbenzyl)-4beta-[2-(trimethylsilyl)ethynyl]azetidin-2-one (XXV), which is deprotected with tetrabutylammonium fluoride giving the free acetylene derivative (XXVI). The partial reduction of (XXVI) with H2 over Pd-CaCO3-PbO yields the corresponding ethylene compound (XXVII), which is hydroxylated with disiamylborane (DSB) to give the 2-hydroxyethylazetidinone (XXVIII). The protection of (XXVIII) with tert-butyldimethylsilyl chloride yields the silylated compound (XXIX), which is treated with Na-NH3 to afford 3alpha-ethyl-4beta-[2-(tert-butyldimethylsilyloxy)ethyl]azetidin-2-one (XXX). The protection of (XXX) with tert-butyldimethylsilyl chloride as before gives the fully silylated compound (XXXI), which is submitted to a controlled hydrolysis yielding 3alpha-ethyl-4beta-(2-hydroxyethyl)-1-(tert-butyldimethylsilyl)azetidin-2-one (XXXII). The oxidation of (XXXII) with CrO3 - pyridine gives the acetic acid derivative (XXXIII), which is deprotected to afford 2-(3alpha-ethyl-2-oxoazetidin-4beta-yl)acetic acid (XXXIV). The reaction of (XXXIV) with carbonyldiimidazole (XXXV) gives the corresponding imidazolide (XXXVI), which is condensed with magnesium 4-nitrobenzyl malonate (XXXVII) yielding 4-nitrobenzyl 4-(3alpha-ethyl-2-oxoazetidin-4beta-yl)-3-oxobutanoate (XXXVIII). The diazotation of (XXXVIII) with 4-azidobenzoic acid (XXXIX) gives the 2-diazo-3-oxobutanoate derivative (XL), which is finally cyclized to carbapen derivative (XII) in the presence of rhodium acetate. The reaction of (XII) with diphenyl chlorophosphate affords the enol phosphate (XIII), which is condensed with N-acetylcysteamine (XIV) to give 4-nitrobenzyl ester of PS-5 (XV). Finally, this compound is deprotected by hydrogenation with H2 over Pd/C.
| 【1】 Shibasaki, M.; Ishida, Y.; Iwasaki, G.; Iimori, T.; Asymmetric synthesis of the carbapenem antibiotic (+)-PS-5. J Org Chem 1987, 52, 15, 3488-9. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 16074 | Diphenyl phosphoryl chloride; 1,1'-Diphenylphosphoryl chloride; Chlorodiphenyl Phosphate; Diphenyl chlorophosphate; Diphenylchlorophosphate | 2524-64-3 | C12H10ClO3P | 详情 | 详情 | |
| 44204 | N,N-diethyl-2-propanamine; N,N-diethyl-N-isopropylamine | C7H17N | 详情 | 详情 | ||
| (XII) | 20032 | 4-nitrobenzyl (5R,6R)-6-ethyl-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate | C16H16N2O6 | 详情 | 详情 | |
| (XIII) | 20033 | 4-nitrobenzyl (5R,6R)-3-[(diphenoxyphosphoryl)oxy]-6-ethyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C28H25N2O9P | 详情 | 详情 | |
| (XIV) | 20034 | N-(2-sulfanylethyl)acetamide | 1190-73-4 | C4H9NOS | 详情 | 详情 |
| (XV) | 20035 | 4-nitrobenzyl (5R,6R)-3-[[2-(acetamido)ethyl]sulfanyl]-6-ethyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C20H23N3O6S | 详情 | 详情 | |
| (XIX) | 20039 | S-phenyl butanethioate | C10H12OS | 详情 | 详情 | |
| (XX) | 20040 | (E)-1-(9-borabicyclo[3.3.1]non-9-yloxy)-1-butenyl phenyl sulfide; 9-[[(E)-1-(phenylsulfanyl)-1-butenyl]oxy]-9-borabicyclo[3.3.1]nonane | C18H25BOS | 详情 | 详情 | |
| (XXI) | 20041 | (1S)-1-phenyl-N-[(Z)-3-(trimethylsilyl)-2-propynylidene]-1-ethanamine; N-[(1S)-1-phenylethyl]-N-[(Z)-3-(trimethylsilyl)-2-propynylidene]amine | C14H19NSi | 详情 | 详情 | |
| (XXII) | 20042 | (1S)-1-phenyl-1-ethanamine; (1S)-1-phenylethylamine | C8H11N | 详情 | 详情 | |
| (XXIII) | 20043 | 3-(trimethylsilyl)-2-propynal | C6H10OSi | 详情 | 详情 | |
| (XXIV) | 20044 | S-phenyl (2R,3S)-2-ethyl-3-[[(1S)-1-phenylethyl]amino]-5-(trimethylsilyl)-4-pentynethioate | C24H31NOSSi | 详情 | 详情 | |
| (XXV) | 20045 | (3R,4S)-3-ethyl-1-[(1S)-1-phenylethyl]-4-[2-(trimethylsilyl)ethynyl]-2-azetidinone | C18H25NOSi | 详情 | 详情 | |
| (XXVI) | 20046 | (3R,4S)-3-ethyl-4-ethynyl-1-[(1S)-1-phenylethyl]-2-azetidinone | C15H17NO | 详情 | 详情 | |
| (XXVII) | 20047 | (3R,4R)-3-ethyl-1-[(1S)-1-phenylethyl]-4-vinyl-2-azetidinone | C15H19NO | 详情 | 详情 | |
| (XXVIII) | 20048 | (3R,4R)-3-ethyl-4-(2-hydroxyethyl)-1-[(1S)-1-phenylethyl]-2-azetidinone | C15H21NO2 | 详情 | 详情 | |
| (XXIX) | 20049 | (3R,4R)-4-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-3-ethyl-1-[(1S)-1-phenylethyl]-2-azetidinone | C21H35NO2Si | 详情 | 详情 | |
| (XXX) | 20050 | (3R,4R)-4-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-3-ethyl-2-azetidinone | C13H27NO2Si | 详情 | 详情 | |
| (XXXI) | 20051 | (3R,4R)-1-[tert-butyl(dimethyl)silyl]-4-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-3-ethyl-2-azetidinone | C19H41NO2Si2 | 详情 | 详情 | |
| (XXXII) | 20052 | (3R,4R)-1-[tert-butyl(dimethyl)silyl]-3-ethyl-4-(2-hydroxyethyl)-2-azetidinone | C13H27NO2Si | 详情 | 详情 | |
| (XXXIII) | 20053 | 2-[(2R,3R)-1-[tert-butyl(dimethyl)silyl]-3-ethyl-4-oxoazetidinyl]acetic acid | C13H25NO3Si | 详情 | 详情 | |
| (XXXIV) | 20054 | 2-[(2R,3R)-3-ethyl-4-oxoazetidinyl]acetic acid | C7H11NO3 | 详情 | 详情 | |
| (XXXV) | 11353 | 1,1'-Carbonyldiimidazole; Di(1H-imidazol-1-yl)methanone; N,N-Carbonyldiimidazole; 1,1'-Carbonylbis(1H-imidazole) | 530-62-1 | C7H6N4O | 详情 | 详情 |
| (XXXVI) | 20056 | (3R,4R)-3-ethyl-4-[2-(1H-imidazol-1-yl)-2-oxoethyl]-2-azetidinone | C10H13N3O2 | 详情 | 详情 | |
| (XXXVII) | 20057 | Malonic acid monoethyl ester magnesium salt | C20H16MgN2O12 | 详情 | 详情 | |
| (XXXVIII) | 20058 | 4-nitrobenzyl 4-[(2R,3R)-3-ethyl-4-oxoazetidinyl]-3-oxobutanoate | C16H18N2O6 | 详情 | 详情 | |
| (XXXIX) | 20059 | 4-azidobenzoic acid | 6427-66-3 | C7H5N3O2 | 详情 | 详情 |
| (XL) | 20060 | (2R,3R)-2-Diazo-4-(3-ethyl-4-oxoazetidin-2-yl)-3-oxobutyric acid 4-nitrobenzyl ester | C16H16N4O6 | 详情 | 详情 |