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【结 构 式】 
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【分子编号】54627 【品名】(2S,3S)-2-[[(benzyloxy)carbonyl](methyl)amino]-3-methylpentanoic acid 【CA登记号】 |
【 分 子 式 】C15H21NO4 【 分 子 量 】279.33608 【元素组成】C 64.5% H 7.58% N 5.01% O 22.91% |
合成路线1
该中间体在本合成路线中的序号：(II)The methylation of N-(benzyloxycarbonyl)-L-isoleucine (I) with Me-I and NaH in THF gives the N-methyl derivative (II), which is reduced with BH3 in THF to yield the isoleucinol (III). The oxidation of (III) with SO3/pyridine in DMSO affords the isoleucinal (IV), which is condensed with tert-butyl acetate (V) by means of BuLi and THF to afford the chiral beta-hydroxyheptanoate (VI). Finally, this compound is O-methylated by means of diazomethane and BF3 in ethyl ether/dichloromethane and N-deprotected by hydrogenation with H2 over Pd/C in ethyl acetate/methanol to provide the desired intermediate, the chiral tert-butyl heptanoate (VII).
| 【1】 Pettit, G.R.; Singh, S.B.; Williams, M.D.; Herald, D.L.; Hogan, F.; Burkett, D.D.; Clewlow, P.J.; The absolute configuration and synthesis of natural (-)-Dolastatin 10. J Am Chem Soc 1989, 111, Suppl. 3, 5463. |
| 【2】 Pettit, G.R.; Srirangam, J.K.; Singh, S.B.; Williams, M.D.; Herald, D.L.; Barkóczy, J.; Kantoci, D.; Hogan, F.; Dolastatins 24. Synthesis of (-)-dolastatin 10. X-Ray molecular structure of N,N-dimethylvalyl-valyl-dolaisoleucine tert-butyl ester. J Chem Soc Perkins Trans I 1996, 8, Suppl. 3, 859-63. |
| 【3】 Pettit, G.R.; Singh, S.B. (Arizona State University); Synthesis of dolastatin 10. US 4978744 . |
| 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) | 23508 | (2S,3S)-2-[[(benzyloxy)carbonyl]amino]-3-methylpentanoic acid | 3160-59-6 | C14H19NO4 | 详情 | 详情 |
| (II) | 54627 | (2S,3S)-2-[[(benzyloxy)carbonyl](methyl)amino]-3-methylpentanoic acid | C15H21NO4 | 详情 | 详情 | |
| (III) | 54628 | benzyl (1S,2S)-1-(hydroxymethyl)-2-methylbutyl(methyl)carbamate | C15H23NO3 | 详情 | 详情 | |
| (IV) | 54629 | benzyl (1S,2S)-1-formyl-2-methylbutyl(methyl)carbamate | C15H21NO3 | 详情 | 详情 | |
| (V) | 13597 | 2,2-Dimethylpropanoyl chloride; Pivaloyl chloride | 3282-30-2 | C5H9ClO | 详情 | 详情 |
| (VI) | 54630 | tert-butyl (3R,4S,5S)-4-[[(benzyloxy)carbonyl](methyl)amino]-3-hydroxy-5-methylheptanoate | C21H33NO5 | 详情 | 详情 | |
| (VII) | 23514 | tert-butyl (3R,4S,5S)-3-methoxy-5-methyl-4-(methylamino)heptanoate | C14H29NO3 | 详情 | 详情 |