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【结 构 式】 
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【分子编号】23501 【品名】benzyl propionate 【CA登记号】122-63-4 |
【 分 子 式 】C10H12O2 【 分 子 量 】164.20408 【元素组成】C 73.15% H 7.37% O 19.49% |
合成路线1
该中间体在本合成路线中的序号：(II)1) The reaction of tert-butoxycarbonyl-L-prolinal (I) with benzyl propionate (II) by means of lithium diisopropylamide (LDA) in THF gives a mixture of isomers that is separated by flash chromatography, yielding the (2R,3R)-isomer (III). The methylation of (III) with diazomethane and boron trifluoride ethearate or NaH and methyl iodide affords the methoxy derivative (IV), which is deprotected with HCl in dioxane, giving (V). The condensation of (V) with tripeptide (VI) by means of diethyl phosphorocyanidate (DEPC) in DMF yields the tetrapeptide benzyl ester (VII), which is finally debenzylated by hydrogenolysis over Pd/C in tert-butanol and amidated with 2-phenylethylamine (VIII) and DEPC and triethylamine in DMF.
| 【1】 Tsukagoshi, S.; Sakakibara, K.; Gondo, M.; Natsume, T.; Mikami, T.; Kobayashi, M.; Miyazaki, K.; Synthesis and antitumor activity of novel dolastat. Chem Pharm Bull 1995, 43, 10, 1706. |
| 【2】 Castañer, J.; Leeson, P.; Hoshi, A.; TZT-1027. Drugs Fut 1999, 24, 4, 404. |
| 【3】 Sakakibara, K.; Gondo, M.; Miyazaki, K. (Teikoku Hormone Manufacturing Co., Ltd.); Novel tetrapeptide derivs.. EP 0598129; JP 1993503479; US 5654399; WO 9303054 . |
| 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) | 16724 | tert-Butyl (2S)-2-formyltetrahydro-1H-pyrrole-1-carboxylate; tert-Butoxycarbonyl-L-prolinal | 69610-41-9 | C10H17NO3 | 详情 | 详情 |
| (II) | 23501 | benzyl propionate | 122-63-4 | C10H12O2 | 详情 | 详情 |
| (III) | 23502 | tert-butyl (2S)-2-[(1R,2R)-3-(benzyloxy)-1-hydroxy-2-methyl-3-oxopropyl]-1-pyrrolidinecarboxylate | C20H29NO5 | 详情 | 详情 | |
| (IV) | 23503 | tert-butyl (2S)-2-[(1R,2R)-3-(benzyloxy)-1-methoxy-2-methyl-3-oxopropyl]-1-pyrrolidinecarboxylate | C21H31NO5 | 详情 | 详情 | |
| (V) | 23504 | benzyl (2R,3R)-3-methoxy-2-methyl-3-[(2S)pyrrolidinyl]propanoate | C16H23NO3 | 详情 | 详情 | |
| (VI) | 23505 | (3R,4S,5S)-4-[((2S)-2-[[(2S)-2-(dimethylamino)-3-methylbutanoyl]amino]-3-methylbutanoyl)(methyl)amino]-3-methoxy-5-methylheptanoic acid | C22H43N3O5 | 详情 | 详情 | |
| (VII) | 23506 | benzyl (2R,3R)-3-((2S)-1-[(3R,4S,5S)-4-[((2S)-2-[[(2S)-2-(dimethylamino)-3-methylbutanoyl]amino]-3-methylbutanoyl)(methyl)amino]-3-methoxy-5-methylheptanoyl]pyrrolidinyl)-3-methoxy-2-methylpropanoate | C38H64N4O7 | 详情 | 详情 | |
| (VIII) | 18333 | Phenethylamine; 2-Phenyl-1-ethanamine | 64-04-0 | C8H11N | 详情 | 详情 |