Enantiomeric Scaffolds for Organic Synthesis

用于有机合成的对映体支架

• 批准号: 6780416
• 负责人: LANNY S LIEBESKIND
• 金额: $ 29.59万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-12-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6780416
• 关键词: chemical addition; chemical substitution; chemical synthesis; covalent bond; metal complex; molybdenum; nitrogenous heterocyclic compound; stereochemistry

DESCRIPTION (provided by applicant): Described herein are the design and development of easily prepared molybdenum pi-complexes of unsaturated oxygen and nitrogen heterocycles (eta-3-pyranyl, eta-3-pyridinyl, and others) of high enantiopurity, which can be richly functionalized then demetalated in a regio- and stereocontrolled fashion. From a common chiral scaffold, demetalation coincident with functionalization will be studied by three core protocols: sequential functionalization allowing attachment of multiple substituents, [5+2] and [5+3] cycloaddition providing access to oxa- and aza-bridged bicyclics, and [4+2] cycloadditions with alkenyl substituted eta-3-pyranyls and eta-3-pyridinyls giving a novel entry to ring-fused heterocycles. In principle, these pi-complexes function as chiral scaffolds of high enantiopurity for the rapid assembly of substituted oxygen and nitrogen heterocyclic systems of known or potential medicinal value. In addition to the obvious exploitation of solution-based protocols, the metal complex "scaffold" approach should be particularly amenable to structure-activity-relationship studies using parallel synthesis technologies. This "enantiomerically-pure scaffold" strategy, if developed to its fullest potential, could hold great promise for rapid SAR studies of substituted oxygen- and nitrogen heterocyclic systems of high enantiopurity.

描述(由申请人提供)：这里描述了易于制备的高对映体纯度的不饱和氧杂环和氮杂环(ETA-3-吡喃基、ETA-3-吡啶基等)的钼PI络合物的设计和开发，其可以被丰富的官能化，然后以区域和立体控制的方式去金属化。从一个常见的手性支架出发，与官能化相一致的脱金属反应将通过三个核心协议进行研究：允许连接多个取代基的顺序官能化，提供获得氧杂桥双环的[5+2]和[5+3]环加成反应，以及与烯基取代的ETA-3-吡喃和ETA-3-吡啶的[4+2]环加成反应，获得新的环稠合杂环。原则上，这些pi-络合物作为高对映体纯度的手性支架，用于快速组装取代氧和氮杂环。 已知或潜在药用价值的系统。 除了明显利用基于解决方案的协议外，金属复合体还是一个“脚手架” 方法应特别适合于使用平行的结构-活动-关系研究 合成技术。这种“纯对映体”策略，如果发展到最充分的话 潜力，可能为取代氧和氮的快速合成孔径雷达研究带来巨大的希望 具有高对映体纯度的杂环体系。