Metalloenamine reactions: Synthesis of Halichlorine

描述（由申请人提供）： 大多数候选药物是含胺化合物。因此，开发有效和立体选择性地制备胺的新方法是一个持续的目标。Ellman小组一直在探索使用容易获得的简单醛和酮的亚磺酰亚胺不对称地生成胺化合物的方法。他们最近报道了通过将亚胺转化为金属烯胺，然后使它们与醛反应，这些亚磺酰基亚胺首次用作亲核试剂。该提案计划扩展这种金属烯胺化学，并将其应用于一种潜在的抗炎和抗癌剂Halichlorine的正式合成。合成涉及将这些手性金属烯胺以共轭方式添加到前手性迈克尔受体。这将允许从一种手性助剂快速扩链和选择性地产生多个立体中心。如果成功的话，可以使用这种方法构建在许多生物碱中发现的各种各样的结构基序。

DESCRIPTION (provided by applicant): The majority of drug candidates are amine-containing compounds. Thus the development of new methods to make amines efficiently and stereoselectively is a continuing goal. The Ellman group has been exploring ways to generate amine compounds asymmetrically using readily available sulfinyl imines of simple aldehydes and ketones. They have recently reported the first use of these sulfinyl imines as nucleophiles by converting the imine into a metalloenamine, and then reacting them with aldehydes. This proposal plans to extend this metalloenamine chemisty and apply it to the formal synthesis of Halichlorine, a potential anti-inflammatory and anti-cancer agent. The synthesis involves adding these chiral metailoenamines to prochiral Michael acceptors in a conjugate fashion. This would allow for rapid chain extension and selective generation of multiple stereocenters from one chiral auxiliary. If successful, a diverse array of structural motifs found in many alkaloids can be constructed using this methodology.