|
【结 构 式】 
|
【分子编号】49098 【品名】 【CA登记号】 |
【 分 子 式 】C21H23N5O6 【 分 子 量 】441.44372 【元素组成】C 57.14% H 5.25% N 15.86% O 21.75% |
合成路线1
该中间体在本合成路线中的序号：(VI)-(Benzyloxycarbonyl)-L-leucine (I) was activated as the mixed anhydride with isobutyl chloroformate and then coupled with N,O-dimethylhydroxylamine to produce the N-methoxyamide (II). Reduction of (II) with LiAlH4 at -78 C furnished aldehyde (III), which was converted to the corresponding diethyl acetal (IV) upon treatment with triethyl orthoformate. Subsequent hydrogenolytic removal of the benzyloxycarbonyl group of (IV) afforded leucinal diethylacetal (V). Coupling of N-Fmoc-nitroarginine (VI) with aminoacetal (V) via activation as the mixed anhydride with isobutyl chloroformate provided the protected dipeptide aldehyde (VII). The Fmoc protecting group of (VII) was then cleaved by using diethylamine in DMF-EtOAc to provide the intermediate (VIII).
| 【1】 Iqbal, M.; et al.; Potent inhibitors of proteasome. J Med Chem 1995, 38, 13, 2276. |
| 【2】 Iqbal, M.; Diebold, J.; Siman, R.; Chatterjee, S.; Kauer, J.C. (Cephalon, Inc.); Multicatalytic protease inhibitors. JP 1998507465; JP 2000290197; WO 9614857 . |
| 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) | 22838 | (2S)-2-[[(benzyloxy)carbonyl]amino]-4-methylpentanoic acid | C14H19NO4 | 详情 | 详情 | |
| (II) | 49094 | benzyl (1S)-1-[[methoxy(methyl)amino]carbonyl]-3-methylbutylcarbamate | C16H24N2O4 | 详情 | 详情 | |
| (III) | 49095 | benzyl (1S)-1-formyl-3-methylbutylcarbamate | C14H19NO3 | 详情 | 详情 | |
| (IV) | 49096 | benzyl (1S)-1-(diethoxymethyl)-3-methylbutylcarbamate | C18H29NO4 | 详情 | 详情 | |
| (V) | 49097 | (2S)-1,1-diethoxy-4-methyl-2-pentanamine; (1S)-1-(diethoxymethyl)-3-methylbutylamine | C10H23NO2 | 详情 | 详情 | |
| (VI) | 49098 | C21H23N5O6 | 详情 | 详情 | ||
| (VII) | 49099 | C31H44N6O7 | 详情 | 详情 | ||
| (VIII) | 49100 | C16H34N6O5 | 详情 | 详情 |