Metalloenamine reactions: Synthesis of Halichlorine

金属烯胺反应：卤氯的合成

• 批准号: 6882742
• 负责人: STEVEN J O'MALLEY
• 金额: $ 3.9万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-22 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6882742
• 关键词: alkaloids; antiinflammatory agents; antineoplastics; chemical conjugate; chemical structure function; chemical synthesis; chlorine; drug design /synthesis /production; imines; intermolecular interaction; organometallic compounds; postdoctoral investigator; stereoisomer

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.

描述(由申请人提供)： 大多数候选药物都是含有胺的化合物。因此，开发高效和立体选择性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单醛和酮的亚氨基亚胺不对称生成胺化合物的方法。他们最近首次报道了亚胺作为亲核剂的用途，方法是将亚胺转化为金属烯胺，然后将它们与醛反应。这项提议计划扩展这种金属烯胺化学，并将其应用于卤化氯的正式合成，卤化氯是一种潜在的抗炎和抗癌药物。合成包括以共轭方式将这些手性间胺加到前手性Michael受体上。这将允许快速扩链和从一个手性助剂选择性地产生多个立体中心。如果成功，可以使用这种方法构建在许多生物碱中发现的各种结构基序。