Gulevich Anton V, Balenkova Elizabeth S, Nenajdenko Valentine G
Department of Chemistry, Moscow State University, Leninskije gory, 119992 Moscow, Russia.
J Org Chem. 2007 Oct 12;72(21):7878-85. doi: 10.1021/jo071030o. Epub 2007 Sep 13.
The first example of a diastereoselective thio-Ugi reaction with chiral alpha-methylbenzylamine is described. The reaction results in formation of two diastereomers of thioamides, the major of which was isolated. We have found that under similar conditions stereochemical results of the thio-Ugi reaction are opposite to stereochemical results of the Ugi reaction. Several chiral thioamides were synthesized. The reaction of thioamides with ammonia results in substituted amidines, which can be cyclized to imidazole derivatives in aqueous HCl. The synthesis of chiral imidazole derivatives was elaborated. Using certain approaches, both isomers of a key synthon in the synthesis of SB203386 (an orally bioactive HIV-1 protease inhibitor) were prepared. The scope, limitations, and stereochemistry of the approach are discussed.
描述了首例使用手性α-甲基苄胺的非对映选择性硫代乌吉反应。该反应生成了硫代酰胺的两种非对映异构体，其中主要的异构体被分离出来。我们发现，在相似条件下，硫代乌吉反应的立体化学结果与乌吉反应的立体化学结果相反。合成了几种手性硫代酰胺。硫代酰胺与氨反应生成取代脒，其在盐酸水溶液中可环化生成咪唑衍生物。阐述了手性咪唑衍生物的合成。使用某些方法制备了SB203386（一种口服生物活性HIV-1蛋白酶抑制剂）合成中关键合成子的两种异构体。讨论了该方法的适用范围、局限性和立体化学。
