Engstrom Kenneth, Henry Rodger, Hollis L Steven, Kotecki Brian, Marsden Ian, Pu Yu-Ming, Wagaw Seble, Wang Weifeng
Department of Process Chemistry, Global Pharmaceutical Research and Development, Abbott Laboratories, 1401 Sheridan Road, North Chicago, IL 60064-6290, USA.
J Org Chem. 2006 Jul 7;71(14):5369-72. doi: 10.1021/jo060737s.
A stereoselective synthesis of the hydroxyethylene dipeptide isostere 1 is described. The route employs a substrate-directed kinetic protonation of an alpha/gamma-substituted lactone to afford the desired stereochemistry. A method for converting the diastereomerically enriched intermediate lactone to the ring-open form with retention of stereochemistry is demonstrated. A novel procedure for utilizing N,N-dibromo-5,5-dimethylhydantoin in Hofmann rearrangements is disclosed. This route was used to prepare amino alcohol 1, the core portion of the HIV protease inhibitor A-792611, in 46% yield from phenylalanine-derived epoxide 2.
描述了羟基乙烯二肽电子等排体1的立体选择性合成。该路线采用α/γ-取代内酯的底物导向动力学质子化反应以提供所需的立体化学结构。展示了一种将非对映体富集的中间体内酯转化为具有立体化学结构保留的开环形式的方法。公开了一种在霍夫曼重排中利用N,N-二溴-5,5-二甲基乙内酰脲的新方法。该路线用于从苯丙氨酸衍生的环氧化物2制备氨基醇1（HIV蛋白酶抑制剂A-792611的核心部分），产率为46%。
