Asymmetric Synthesis of Highly Substituted Azapolycyclic Compounds via 2-Alkenyl Sulfoximines: Potential Scaffolds for Peptide Mimetics

The application of metalated, enantiomerically pure acyclic and cyclic 2-alkenyl sulfoximines for
the synthesis of highly substituted aza(poly)cyclic ring systems is described. The method relies on a one-pot combination of a reagent-controlled allyl transfer reaction to α- or β-amino aldehydes, followed by a
Michael-type cyclization of the intermediate vinyl sulfoximines generated in the first step. The sulfur-free
target compounds are preferentially obtained by samarium iodide treatment of the sulfonimidoyl substituted
heterocycles. In addition to this methodological work, initial results on the biological activity of selected
examples are reported. Furthermore, a concept for the transformation of peptidic lead structures into non-peptide mimetics is described, and the relevance of the new approach to highly substituted azaheterocycles
in this context is discussed.

本文报道了金属化、对映纯的无环与环状2-烯基亚砜亚胺（sulfoximines）在高取代氮杂（多）环体系合成中的应用。该方法依托一锅法策略：先经试剂调控的烯丙基转移反应将底物与α-或β-氨基醛结合，随后对第一步生成的中间体乙烯基亚砜亚胺进行迈克尔型环化反应。目标无硫产物可通过碘化钐处理磺酰亚胺基取代杂环高效制备。除上述方法学研究外，本文还报道了部分代表性化合物的初步生物活性测试结果。此外，本文阐述了将肽类先导结构转化为非肽模拟物的新思路，并探讨了该高取代氮杂杂环合成新方法在该研究背景下的应用价值。