【结 构 式】 |
【分子编号】25726 【品名】tert-butyl (4S,5R)-4-benzyl-5-[2-([(1S)-1-[(1S)-2-([(1S)-1-[(benzyloxy)carbonyl]-2-methylpropyl]oxy)-1-methyl-2-oxoethyl]octyl]oxy)-2-oxoethyl]-1,3-oxazolidine-3-carboxylate 【CA登记号】 |
【 分 子 式 】C40H57NO9 【 分 子 量 】695.89392 【元素组成】C 69.04% H 8.26% N 2.01% O 20.69% |
合成路线1
该中间体在本合成路线中的序号:(XVI)Treatment of N-Boc-L-phenylalanine (XI) with carbonyl diimidazole, followed by condensation with the lithium enolate of ethyl acetate provided the beta-ketoester (XII). Then, reduction with NaBH4 in EtOH at -78 C furnished the anti aminoalcohol (XIII) as the major isomer. Subsequent reaction with formaldehyde in the presence of p-toluenesulfonic acid in boiling toluene produced the cis oxazolidine (XIV). Basic hydrolis of the ester group yielded carboxylic acid (XV) which, after activation as the mixed anhydride with 2,4,6-trichlorobenzoyl chloride (VI), was coupled to hydroxyester (X) to give triester (XVI). Reduction of the oxazolidine with NaBH3CN in the presence of trifluoroacetic acid afforded the N-methylated derivative (XVII). Then, hydrogenolysis of the benzyl ester in the presence of Pd/C produced acid (XVIII), which was finally cyclized using DPPA.
【1】 Wagner, B.; et al.; Total synthesis and conformational studies of hapalosin, N-desmethylhapalosin and 8-deoxyhapalosin. Bioorg Med Chem 1999, 7, 5, 737. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(VI) | 25718 | 2,4,6-trichlorobenzoyl chloride | 4136-95-2 | C7H2Cl4O | 详情 | 详情 |
(X) | 25722 | (1S)-1-[(benzyloxy)carbonyl]-2-methylpropyl (2S,3R)-3-hydroxy-2-methyldecanoate | C23H36O5 | 详情 | 详情 | |
(XI) | 12874 | (2R)-2-[(tert-Butoxycarbonyl)amino]-3-phenylpropionic acid; N-alpha-t-BOC-L-Phenylalanine | 13734-34-4 | C14H19NO4 | 详情 | 详情 |
(XII) | 12876 | ethyl (4S)-4-[(tert-butoxycarbonyl)amino]-3-oxo-5-phenylpentanoate | C18H25NO5 | 详情 | 详情 | |
(XIII) | 25723 | ethyl (3R,4S)-4-[(tert-butoxycarbonyl)amino]-3-hydroxy-5-phenylpentanoate | C18H27NO5 | 详情 | 详情 | |
(XIV) | 25724 | tert-butyl (4S,5R)-4-benzyl-5-(2-ethoxy-2-oxoethyl)-1,3-oxazolidine-3-carboxylate | C19H27NO5 | 详情 | 详情 | |
(XV) | 25725 | 2-[(4S,5R)-4-benzyl-3-(tert-butoxycarbonyl)-1,3-oxazolidin-5-yl]acetic acid | C17H23NO5 | 详情 | 详情 | |
(XVI) | 25726 | tert-butyl (4S,5R)-4-benzyl-5-[2-([(1S)-1-[(1S)-2-([(1S)-1-[(benzyloxy)carbonyl]-2-methylpropyl]oxy)-1-methyl-2-oxoethyl]octyl]oxy)-2-oxoethyl]-1,3-oxazolidine-3-carboxylate | C40H57NO9 | 详情 | 详情 | |
(XVII) | 25727 | (1S)-1-[(benzyloxy)carbonyl]-2-methylpropyl (2S,3S)-3-[[(3R,4S)-3-hydroxy-4-(methylamino)-5-phenylpentanoyl]oxy]-2-methyldecanoate | C35H51NO7 | 详情 | 详情 | |
(XVIII) | 25728 | (2S)-2-[((2S,3S)-3-[[(3R,4S)-3-hydroxy-4-(methylamino)-5-phenylpentanoyl]oxy]-2-methyldecanoyl)oxy]-3-methylbutyric acid | C28H45NO7 | 详情 | 详情 |