【结 构 式】 |
【分子编号】54630 【品名】tert-butyl (3R,4S,5S)-4-[[(benzyloxy)carbonyl](methyl)amino]-3-hydroxy-5-methylheptanoate 【CA登记号】 |
【 分 子 式 】C21H33NO5 【 分 子 量 】379.49676 【元素组成】C 66.46% H 8.76% N 3.69% O 21.08% |
合成路线1
该中间体在本合成路线中的序号:(VI)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 |
合成路线2
该中间体在本合成路线中的序号:(X)Coupling of diamine (IX) with the Boc-protected diamino acid (X) by means of DCC and HOBt gives rise to amide (XI). The title compound is finally obtained by acidic cleavage of the N-Boc protecting groups of (XI).
【1】 Roberts, C.; et al.; Discovery af a new class of broad-spectrum antifungal compounds that target the minor groove of DNA. 28th Natl Med Chem Symp (June 8 2002, San Diego) 2002, Abst 67. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(IX) | 54629 | benzyl (1S,2S)-1-formyl-2-methylbutyl(methyl)carbamate | C15H21NO3 | 详情 | 详情 | |
(X) | 54630 | tert-butyl (3R,4S,5S)-4-[[(benzyloxy)carbonyl](methyl)amino]-3-hydroxy-5-methylheptanoate | C21H33NO5 | 详情 | 详情 | |
(XI) | 54631 | (1S)-2-hydroxy-1,2,2-triphenylethyl propionate | C23H22O3 | 详情 | 详情 |