|
【结 构 式】 
|
【分子编号】52727 【品名】benzyl (2S,4S)-4-{[tert-butyl(dimethyl)silyl]oxy}-2,5-dimethyl-3-oxohexanoate 【CA登记号】 |
【 分 子 式 】C21H34O4Si 【 分 子 量 】378.58406 【元素组成】C 66.62% H 9.05% O 16.9% Si 7.42% |
合成路线1
该中间体在本合成路线中的序号：(XVI)The protected dipeptide (XIV) was prepared by coupling between L-proline benzyl ester (XII) and N-Boc-L-leucine (XIII) in the presence of DCC and HOBt. Acidic Boc group cleavage in (XIV) then gave amine (XV). The unstable keto acid (XVII) was obtained by hydrogenolysis of the epimeric benzyl esters (XVI), and subsequently coupled to the dipeptide ester (XV) by means of HBTU to afford the keto amide (XVIII) as a diastereomeric mixture. Desilylation of (XVIII) with tetrabutylammonium fluoride furnished the deprotected alcohol (XIX), which was further esterified with the protected isostatine (XI) leading to depsipeptide (XX). Then, removal of the O-silyl and N-Boc protecting groups of (XX) under acidic conditions provided intermediate (XXI)
| 【1】 Jou, G.; Gonzalez, I.; Albericio, F.; Lloyd-Williams, P.; Giralt, E.; Total synthesis of dehydrodidemnin B. Use of uronium and phosphonium salt coupling reagents in peptide synthesis in solution. J Org Chem 1997, 62, 2, 354. |
| 【2】 Giralt Lledo, E.; Albericio Palomera, F.; Lloyd-Williams, P.; Gonzalez Valcarcel, I.; Jou Prat, G.; Gomez Gonzalez, A.; Manzanares Secades, I. (PharmaMar, SA); Process for the preparation of didemnine A. ES 2102322 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 50793 | benzyl (2S)-1-((2S)-2-[[(2S,4S)-4-hydroxy-2,5-dimethyl-3-oxohexanoyl]amino]-4-methylpentanoyl)-2-pyrrolidinecarboxylate | C26H38N2O6 | 详情 | 详情 | |
| (XII) | 20930 | benzyl (2S)-2-pyrrolidinecarboxylate | 16652-71-4 | C12H15NO2 | 详情 | 详情 |
| (XIII) | 23663 | (2S)-2-[(tert-butoxycarbonyl)amino]-4-methylpentanoic acid；N-Boc-L-leucine | C11H21NO4 | 详情 | 详情 | |
| (XIV) | 52728 | benzyl (2S)-1-{(2S)-2-[(tert-butoxycarbonyl)amino]-4-methylpentanoyl}-2-pyrrolidinecarboxylate | C23H34N2O5 | 详情 | 详情 | |
| (XV) | 50792 | benzyl (2S)-1-[(2S)-2-amino-4-methylpentanoyl]-2-pyrrolidinecarboxylate | C18H26N2O3 | 详情 | 详情 | |
| (XVI) | 52727 | benzyl (2S,4S)-4-{[tert-butyl(dimethyl)silyl]oxy}-2,5-dimethyl-3-oxohexanoate | C21H34O4Si | 详情 | 详情 | |
| (XVII) | 50791 | (2S,4S)-4-[[tert-butyl(dimethyl)silyl]oxy]-2,5-dimethyl-3-oxohexanoic acid | C14H28O4Si | 详情 | 详情 | |
| (XVIII) | 52729 | benzyl (2S)-1-{(2S)-2-[((2S,4S)-4-{[tert-butyl(dimethyl)silyl]oxy}-2,5-dimethyl-3-oxohexanoyl)amino]-4-methylpentanoyl}-2-pyrrolidinecarboxylate | C32H52N2O6Si | 详情 | 详情 | |
| (XX) | 62535 | benzyl (2S)-1-{(2S,7S,11S,12R)-11-{[tert-butyl(dimethyl)silyl]oxy}-2-isobutyl-7-isopropyl-5,16,16-trimethyl-12-[(1S)-1-methylpropyl]-4,6,9,14-tetraoxo-8,15-dioxa-3,13-diazaheptadec-1-anoyl}-2-pyrrolidinecarboxylate | C45H75N3O10Si | 详情 | 详情 | |
| (XXI) | 62536 | benzyl (2S)-1-{(2S)-2-[((4S)-4-{[(3S,4R,5S)-4-amino-3-hydroxy-5-methylheptanoyl]oxy}-2,5-dimethyl-3-oxohexanoyl)amino]-4-methylpentanoyl}-2-pyrrolidinecarboxylate | C34H53N3O8 | 详情 | 详情 |