Sarabia Francisco, Martín-Gálvez Francisca, García-Castro Miguel, Chammaa Samy, Sánchez-Ruiz Antonio, Tejón-Blanco José F
Department of Biochemistry, Molecular Biology and Organic Chemistry, Faculty of Sciences, University of Malaga, Campus de Teatinos, 29071, Malaga, Spain.
J Org Chem. 2008 Nov 21;73(22):8979-86. doi: 10.1021/jo801728s. Epub 2008 Oct 15.
A new approach to the stereoselective synthesis of polypropionate-type frameworks is reported utilizing reactions of amide-stabilized sulfur ylides with chiral aldehydes. To establish a new strategy for macrolide fragment synthesis, the stereoselectivity of these reactions in the construction of epoxy amides was the most important aspect of this study. In this aspect, we found a strong influence of the protecting groups employed in the starting aldehydes upon the stereochemical outcome of their reactions with the sulfur ylide 1. Thus, numerous aldehydes showed remarkable stereofacial differentiation, providing a major diastereoisomer, in contrast to others that displayed a poor or no stereoselectivity. Despite the difficulties encountered for some cases with respect to their diastereomeric yields, we were able to prepare various stereotetrads and stereopentads, thus enhancing the synthetic value of this new methodology for the preparation of typical polypropionate frameworks found in many natural products, in particular the macrolide class of antibiotics.
报道了一种利用酰胺稳定的硫叶立德与手性醛的反应立体选择性合成聚丙酸酯型骨架的新方法。为了建立大环内酯片段合成的新策略，这些反应在环氧酰胺构建中的立体选择性是本研究最重要的方面。在这方面，我们发现起始醛中使用的保护基对其与硫叶立德1反应的立体化学结果有很大影响。因此，与其他显示出较差或无立体选择性的醛相比，许多醛表现出显著的立体面分化，提供了主要的非对映异构体。尽管在某些情况下，它们的非对映体产率存在困难，但我们能够制备各种立体四元体和立体五元体，从而提高了这种新方法在制备许多天然产物中发现的典型聚丙酸酯骨架，特别是大环内酯类抗生素方面的合成价值。
