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【结 构 式】 
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【分子编号】50778 【品名】ethyl (3S,4R,5S)-4-[(tert-butoxycarbonyl)amino]-3-hydroxy-5-methylheptanoate 【CA登记号】 |
【 分 子 式 】C15H29NO5 【 分 子 量 】303.399 【元素组成】C 59.38% H 9.63% N 4.62% O 26.37% |
合成路线1
该中间体在本合成路线中的序号：(V)Protection of the carboxyl group of Boc-L-threonine (I) with [2-(chloromethoxy)ethyl]trimethylsilane (SEM-Cl) (II) by means of Li2CO3 affords protected threonine (III). Separately, Z-L-tyrosine (IV) is treated with dimethyl sulfate and KOH in THF with tetrabutylammonium hydrogen sulfate as a catalyst to furnish N,O-dimethyl-L-tyrosine (V), which is then converted into secondary amine (VI) by coupling with protected threonine (III) either by means of 2,4,6-trichlorobenzoyl chloride in THF and DMAP in benzene or with isopropenyl chloroformate, Et3N and DMAP, followed by elimination of the carbobenzyloxy group by hydrogenation over Pd/C. Coupling of Z-L-leucine (IX) to L-proline methyl ester (X) by means of DCC, HOBt and NMM in CH2Cl2, followed by hydrolysis with LiOH, affords Z-leucylproline (VII), which is then coupled to amine (VI) by means of BOPCl and Et3N in CH2Cl2, and then subjected to deprotection with hydrofluoric acid in acetonitrile affording intermediate (VIII).
| 【1】 Hamada, Y.; Shioiri, T.; Anti-tumor active cyclic peptide derived from marine organism: Synthesis, conformation and bioactivity. Kagaku Zokan 1990, 118, 31. |
| 【2】 Harris, B.D.; et al.; Synthetic studies of didemnins. II. Approaches to statine diastereomers. Tetrahedron Lett 1987, 28, 25, 2837. |
| 【3】 Hamada, Y.; et al.; Efficient total synthesis of didemnins A and B. J Am Chem Soc 1989, 111, 2, 669. |
| 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) | 50775 | (2R,3S)-2-[(tert-butoxycarbonyl)amino]-3-methylpentanoic acid | C11H21NO4 | 详情 | 详情 | |
| (II) | 44205 | (2-ethoxy-2-oxoethyl)lithium | C4H7LiO2 | 详情 | 详情 | |
| (III) | 50776 | ethyl (4R,5S)-4-[(tert-butoxycarbonyl)amino]-5-methyl-3-oxoheptanoate | C15H27NO5 | 详情 | 详情 | |
| (IV) | 50777 | tert-butyl (1R,2S)-1-formyl-2-methylbutylcarbamate | C11H21NO3 | 详情 | 详情 | |
| (V) | 50778 | ethyl (3S,4R,5S)-4-[(tert-butoxycarbonyl)amino]-3-hydroxy-5-methylheptanoate | C15H29NO5 | 详情 | 详情 | |
| (VI) | 50779 | 2,2,2-trichloro-1-ethanol | C2H3Cl3O | 详情 | 详情 | |
| (VII) | 50780 | 2,2,2-trichloroethyl (3S,4R,5S)-4-[(tert-butoxycarbonyl)amino]-3-hydroxy-5-methylheptanoate | C15H26Cl3NO5 | 详情 | 详情 | |
| (VIII) | 50781 | 2,2,2-trichloroethyl (3S,4R,5S)-4-amino-3-hydroxy-5-methylheptanoate | C10H18Cl3NO3 | 详情 | 详情 | |
| (IX) | 50782 | (2S,3R)-3-(benzyloxy)-2-[(tert-butoxycarbonyl)amino]butyric acid | C16H23NO5 | 详情 | 详情 | |
| (X) | 50783 | 2,2,2-trichloroethyl (3S,4R,5S)-4-[[(2S,3R)-2-amino-3-(benzyloxy)butanoyl]amino]-3-hydroxy-5-methylheptanoate | C21H31Cl3N2O5 | 详情 | 详情 | |
| (XI) | 50788 | (2R)-2-[(tert-butoxycarbonyl)(methyl)amino]-4-methylpentanoic acid | C12H23NO4 | 详情 | 详情 | |
| (XII) | 31819 | (2R)-2-[(tert-butoxycarbonyl)amino]-4-methylpentanoic acid | 16937-99-8 | C11H21NO4 | 详情 | 详情 |
| (XIII) | 50787 | 2,2,2-trichloroethyl (6R,9S,12R,13S)-9-[(1R)-1-(benzyloxy)ethyl]-13-[[tert-butyl(dimethyl)silyl]oxy]-6-isobutyl-2,2,5-trimethyl-12-[(1S)-1-methylpropyl]-4,7,10-trioxo-3-oxa-5,8,11-triazapentadecan-15-oate | C39H66Cl3N3O8Si | 详情 | 详情 | |
| (XIV) | 50784 | 2,2,2-trichloroethyl (6R,9S,12R,13S)-13-[[tert-butyl(dimethyl)silyl]oxy]-9-[(1R)-1-hydroxyethyl]-6-isobutyl-2,2,5-trimethyl-12-[(1S)-1-methylpropyl]-4,7,10-trioxo-3-oxa-5,8,11-triazapentadecan-15-oate | C32H60Cl3N3O8Si | 详情 | 详情 | |
| (XV) | 50747 | (2S)-2-[[(benzyloxy)carbonyl](methyl)amino]-3-(4-methoxyphenyl)propionic acid | C19H21NO5 | 详情 | 详情 | |
| (XVI) | 39328 | (2S)-2-[[(benzyloxy)carbonyl]amino]-3-(4-hydroxyphenyl)propionic acid | C17H17NO5 | 详情 | 详情 | |
| (XVII) | 50785 | 2,2,2-trichloroethyl (5S,8R,9S,12R,13S)-13-[[tert-butyl(dimethyl)silyl]oxy]-5-(4-methoxybenzyl)-4,8-dimethyl-9-[[(2R)-4-methyl-2-(methylamino)pentanoyl]amino]-12-[(1S)-1-methylpropyl]-3,6,10-trioxo-1-phenyl-2,7-dioxa-4,11-diazapentadecan-15-oate | C46H71Cl3N4O10Si | 详情 | 详情 | |
| (XVIII) | 50786 | (5S,8R,9S,12R,13S)-13-[[tert-butyl(dimethyl)silyl]oxy]-5-(4-methoxybenzyl)-4,8-dimethyl-9-[[(2R)-4-methyl-2-(methylamino)pentanoyl]amino]-12-[(1S)-1-methylpropyl]-3,6,10-trioxo-1-phenyl-2,7-dioxa-4,11-diazapentadecan-15-oic acid | C44H70N4O10Si | 详情 | 详情 |