【结 构 式】 |
【药物名称】 【化学名称】4(S)-(Benzyloxycarbonyl-L-leucyl-L-phenylalanylamino)-6-carbamoyl-2(E)-hexenoic acid ethyl ester 【CA登记号】 【 分 子 式 】C32H42N4O7 【 分 子 量 】594.71414 |
【开发单位】Agouron (Originator) 【药理作用】ANTIINFECTIVE THERAPY, Anti-Rhinovirus Drugs, Antiviral Drugs, Protease Inhibitors |
合成路线1
The condensation of the protected L-glutamine (I) with N,O-dimethylhydroxylamine (II) by means of isobutyl chloroformate and NMM in dichloromethane gives the methoxyamide (III), which is reduced with DIBAL in THF to the aldehyde (IV). The condensation of (IV) with phosphonate (V) by means of NaN(SiMe3)2 in THF yields the carbamoylhexenoate (VI), which is selectively deprotected with HCl in dioxane and condensed with the dipeptide (VII) by means of HOBT, NMM and EDC in dichloromethane to afford the tritylated target compound (VIII). Finally, the trityl group of (VIII) is eliminated with TFA and Et3SiH in dichloromethane.
【1】 Dragovich, P.S.; Babine, R.E.; Webber, S.E.; et al.; Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 1. Michael acceptor structure-activity studies. J Med Chem 1998, 41, 15, 2806. |
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) | 31045 | (2S)-2-[(tert-butoxycarbonyl)amino]-5-oxo-5-(tritylamino)pentanoic acid | C29H32N2O5 | 详情 | 详情 | |
(II) | 13361 | (Methoxyamino)methane; N,O-Dimethylhydroxylamine | 1117-97-1 | C2H7NO | 详情 | 详情 |
(III) | 31046 | tert-butyl (1S)-1-[[methoxy(methyl)amino]carbonyl]-4-oxo-4-(tritylamino)butylcarbamate | C31H37N3O5 | 详情 | 详情 | |
(IV) | 31047 | tert-butyl (1S)-1-formyl-4-oxo-4-(tritylamino)butylcarbamate | C29H32N2O4 | 详情 | 详情 | |
(V) | 10019 | Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate | 867-13-0 | C8H17O5P | 详情 | 详情 |
(VI) | 31048 | ethyl (E,4S)-4-[(tert-butoxycarbonyl)amino]-7-oxo-7-(tritylamino)-2-heptenoate | C33H38N2O5 | 详情 | 详情 | |
(VII) | 31052 | (2S)-2-[((2S)-2-[[(benzyloxy)carbonyl]amino]-4-methylpentanoyl)amino]-3-phenylpropionic acid | C23H28N2O5 | 详情 | 详情 | |
(VII) | 31053 | ethyl (5S,8S,11S,12E)-11-(3-amino-3-oxopropyl)-8-benzyl-5-isobutyl-3,6,9-trioxo-1-phenyl-2-oxa-4,7,10-triaza-12-tetradecen-14-oate | C32H42N4O7 | 详情 | 详情 |