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）： 大多数候选药物是含胺的化合物。因此，开发有效和立体选择性胺的新方法是一个持续的目标。 Ellman组一直在探索使用简单醛和酮的磺胺基因胺不对称地产生胺化合物的方法。他们最近报道了这些磺胺基亚胺作为亲核试剂首次使用，通过将亚胺转化为金属苯胺，然后将它们与醛反应。该建议计划扩展这种金属胺化学物质，并将其应用于潜在的抗炎和抗癌剂Halichlorine的形式合成。该合成涉及以共轭方式将这些手性甲金素胺添加到迈克尔受体的迈克尔受体中。这将允许从一种手性辅助机构快速链扩展和选择性生成多个立体中心。如果成功，可以使用这种方法来构建许多生物碱中发现的各种结构基序。