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【结 构 式】 
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【分子编号】64559 【品名】(2S,3S)-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-3-methylpentanoic acid 【CA登记号】 |
【 分 子 式 】C21H23NO4 【 分 子 量 】353.41796 【元素组成】C 71.37% H 6.56% N 3.96% O 18.11% |
合成路线1
该中间体在本合成路线中的序号：(A)Coupling of threonine benzyl ester (I) to Fmoc-Ile-OH (A) with HBTU, HOBt and DIEA in dichloromethane followed by protection of the hydroxyl group with TBDPS-Cl and imidazole in THF affords protected dipeptide (II). Removal of the Fmoc group of (II) with piperidine/DMF followed by coupling of Fmoc-N-Me-Ile-OH (B) with HBTU, HOBt and DIEA gives fully protected tripeptide (III), which is treated with piperidine/DMF for Fmoc removal and acetylated by means of Ac2O, DIEA in dichloromethane to furnish (IV). Debenzylation of (IV) by hydrogenolysis over Pd/C provides intermediate (V). Addition of 2-bromopropene (VII) and t-BuLi to the Boc-leucine Weinreb amide (VI) in Et2O yields alpha',beta'-unsaturated ketone (VIII), which is oxidized by treatment with H2O2 and DIEA in H2O/benzonitrile/MeOH to afford a mixture of epoxides from which (IX) is separated by column chromatography. Boc deprotection and coupling of peptide (V) with intermediate (IX) by means of TFA, HATU, HOAt, DIEA in dichloromethane, furnishes TBDPS-protected derivative (X), which is finally deprotected by treatment with TBAF in THF.
| 【1】 Sin, N.; et al.; Total synthesis of the potent proteasome inhibitor epoxomicin: A useful tool for understanding proteasome biology. Bioorg Med Chem Lett 1999, 9, 15, 2283. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 64559 | (2S,3S)-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-3-methylpentanoic acid | C21H23NO4 | 详情 | 详情 | |
| (B) | 64679 | (2S,3S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl](methyl)amino]-3-methylpentanoic acid | C22H25NO4 | 详情 | 详情 | |
| (I) | 43023 | benzyl (2S,3R)-2-amino-3-hydroxybutanoate | C11H15NO3 | 详情 | 详情 | |
| (II) | 43022 | benzyl (2S,3R)-3-[[tert-butyl(diphenyl)silyl]oxy]-2-[((2S,3S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-methylpentanoyl)amino]butanoate | C48H54N2O6Si | 详情 | 详情 | |
| (III) | 43024 | benzyl (5S,8S,11S)-11-((1R)-1-[[tert-butyl(diphenyl)silyl]oxy]ethyl)-1-(9H-fluoren-9-yl)-4-methyl-5,8-bis[(1S)-1-methylpropyl]-3,6,9-trioxo-2-oxa-4,7,10-triazadodecan-12-oate | C55H67N3O7Si | 详情 | 详情 | |
| (IV) | 43025 | benzyl (2S,3R)-2-[[(2S,3S)-2-([(2S,3S)-2-[acetyl(methyl)amino]-3-methylpentanoyl]amino)-3-methylpentanoyl]amino]-3-[[tert-butyl(diphenyl)silyl]oxy]butanoate | C42H59N3O6Si | 详情 | 详情 | |
| (V) | 43026 | (2S,3R)-2-[[(2S,3S)-2-([(2S,3S)-2-[acetyl(methyl)amino]-3-methylpentanoyl]amino)-3-methylpentanoyl]amino]-3-[[tert-butyl(diphenyl)silyl]oxy]butyric acid | C35H53N3O6Si | 详情 | 详情 | |
| (VI) | 40395 | tert-butyl (1S)-1-[[methoxy(methyl)amino]carbonyl]-3-methylbutylcarbamate | C13H26N2O4 | 详情 | 详情 | |
| (VII) | 42375 | 2-bromo-1-propene；2-bromopropene;Isopropenyl bromide;a-Methylvinyl bromide | 557-93-7 | C3H5Br | 详情 | 详情 |
| (VIII) | 43027 | tert-butyl (1S)-1-isobutyl-3-methyl-2-oxo-3-butenylcarbamate | C14H25NO3 | 详情 | 详情 | |
| (IX) | 43028 | tert-butyl ((S)-4-methyl-1-((R)-2-methyloxiran-2-yl)-1-oxopentan-2-yl)carbamate；tert-butyl (1S)-3-methyl-1-[[(2R)-2-methyloxiranyl]carbonyl]butylcarbamate | C14H25NO4 | 详情 | 详情 | |
| (X) | 43029 | (2S,3S)-2-[acetyl(methyl)amino]-N-((1S,2S)-1-[[((1S,2R)-2-[[tert-butyl(diphenyl)silyl]oxy]-1-[[((1R)-3-methyl-1-[[(2R)-2-methyloxiranyl]carbonyl]butyl)amino]carbonyl]propyl)amino]carbonyl]-2-methylbutyl)-3-methylpentanamide | C44H68N4O7Si | 详情 | 详情 |