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【结 构 式】 
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【分子编号】12185 【品名】2-Diazo-3-oxo-5-[4-oxo-3-(2-phenoxy-acetamido)-azetidin-2-yl]-pentanoic acid 4-nitro-benzyl ester 【CA登记号】 |
【 分 子 式 】C23H21N5O8 【 分 子 量 】495.44864 【元素组成】C 55.76% H 4.27% N 14.14% O 25.83% |
合成路线1
该中间体在本合成路线中的序号：(XVII)Diazotization of (XVI) with dodecylsulfonyl azide and triethylamine in acetonitrile gives the diazo derivative (XVII), which is cyclized by means of rhodium octanoate in dichloromethane to afford the carbacephem derivative (XVIII). The reaction of (XVIII) with dichlorotriphenoxyphosphine - pyridine in dichloromethane, followed by hydrolysis in acidic medium gives (6R,7S)-7-amino-3-chloro-1-dethia-1-carba-3-cephem-4-carboxylic acid 4-nitrobenzyl ester (XIX). The acylation of (XIX) with the isobutyl anhydride of enamine-protected D-phenylglycine (XX) by means of triethylamine in DMF affords the fully protected compound (XXI), which is finally deprotected by a treatment with Zn and HCl.
| 【1】 Boyer, B.D.; Bodurow, C.C.; Brennan, J.; et al.; An enantioselective synthesis of loracarbef (LY163892/KT3777). Tetrahedron Lett 1989, 30, 18, 2321. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVI) | 12184 | 4-nitrobenzyl 3-oxo-5-[(2R,3S)-4-oxo-3-[(2-phenoxyacetyl)amino]azetanyl]pentanoate | C23H23N3O8 | 详情 | 详情 | |
| (XVII) | 12185 | 2-Diazo-3-oxo-5-[4-oxo-3-(2-phenoxy-acetamido)-azetidin-2-yl]-pentanoic acid 4-nitro-benzyl ester | C23H21N5O8 | 详情 | 详情 | |
| (XVIII) | 12186 | 4-nitrobenzyl (6R,7S)-3-hydroxy-8-oxo-7-[(2-phenoxyacetyl)amino]-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C23H21N3O8 | 详情 | 详情 | |
| (XIX) | 12187 | 4-nitrobenzyl (6R,7S)-7-amino-3-chloro-8-oxo-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C15H14ClN3O5 | 详情 | 详情 | |
| (XX) | 12188 | (2R)-[[(E)-3-Methoxy-1-methyl-3-oxo-1-propenyl]amino](phenyl)ethanoic 2-methylbutyric anhydride | C18H23NO5 | 详情 | 详情 | |
| (XXI) | 12189 | 4-nitrobenzyl (6R,7S)-3-chloro-7-[((2R)-2-[[(E)-3-methoxy-1-methyl-3-oxo-1-propenyl]amino]-2-phenylethanoyl)amino]-8-oxo-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C28H27ClN4O8 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXXVII)Finally, the first total synthesis of stavudine has also been described: Starting from epoxide (XXXIII), readily available in four steps from crotonaldehyde, compound (XXXIV) is obtained after reaction with selenophenol and diethylaluminum fluoride in dichloromethane. Reaction of (XXXIV) with hydrochloric acid in methanol-dichloromethane gives (XXXV), which is acetylated to give (XXXVI). Introduction of silylated thymine (XXIII) catalyzed by tert-butyldimethylsilyl triflate in dichloromethane affords compound (XXXVII), which is converted to (XXXVIII) on treatment with m-chloroperbenzoic acid in dichloromethane. Deprotection of (XXXVIII) provides an anomeric mixture of stavudine and its alpha-anomer (XXXIX).
| 【1】 Gardiner, J.M.; Jung, M.E.; Synthesis of antiviral nucleosides from crotonaldehyde. Part 3. Total synthesis of didehydrodideoxythymidine (d4T). Tetrahedron Lett 1992, 33, 27, 3841-4. |
| 【2】 Robinson, C.; Castaner, J.; Stavudine. Drugs Fut 1994, 19, 10, 925. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXIII) | 12218 | 5-Methyl-2,4-bis[(trimethylsilyl)methyl]pyrimidine | C13H26N2Si2 | 详情 | 详情 | |
| (XXXIII) | 12228 | [3-(2,2-Dimethoxyethyl)-2-oxiranyl]methanol | C7H14O4 | 详情 | 详情 | |
| (XXXIV) | 12229 | (2R,3S)-5,5-Dimethoxy-3-(phenylselanyl)-1,2-pentanediol | C13H20O4Se | 详情 | 详情 | |
| (XXXV) | 12230 | [(2R,3S)-5-Methoxy-3-(phenylselanyl)tetrahydro-2-furanyl]methanol | C12H16O3Se | 详情 | 详情 | |
| (XXXVI) | 12231 | [(2R,3S)-5-methoxy-3-(phenylselanyl)tetrahydro-2-furanyl]methyl acetate | C14H18O4Se | 详情 | 详情 | |
| (XXXVII) | 12185 | 2-Diazo-3-oxo-5-[4-oxo-3-(2-phenoxy-acetamido)-azetidin-2-yl]-pentanoic acid 4-nitro-benzyl ester | C23H21N5O8 | 详情 | 详情 | |
| (XXXVIII) | 12233 | [(2S)-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-2,5-dihydro-2-furanyl]methyl acetate | C12H14N2O5 | 详情 | 详情 |