Methodology towards the synthesis of complex stereochemically dense natural products

复杂立体化学致密天然产物的合成方法

基本信息

批准号：
9257835
负责人：
Evan Rashied Darzi
金额：
$ 5.63万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-03-01 至 2020-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9257835
关键词：
Address Alder plant Alkaloids Alkynes Architecture Chemicals Complex Coupling Diels Alder reaction FDA approved Generations Goals Hand Lead Methodology Methods Molecular Natural Product Drug Natural Products Nitrogen Periodicity Pharmaceutical Preparations Phase Prevalence Reaction Research Route Therapeutic Work cycloaddition diene innovation insight manzamine A piperidine propadiene scaffold small molecule tool

Address Alder plant Alkaloids Alkynes Architecture Chemicals Complex Coupling Diels Alder reaction FDA approved Generations Goals Hand Lead Methodology Methods Molecular Natural Product Drug Natural Products Nitrogen Periodicity Pharmaceutical Preparations Phase Prevalence Reaction Research Route Therapeutic Work cycloaddition diene innovation insight manzamine A piperidine propadiene scaffold small molecule tool

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项目摘要

Project Summary/Abstract The piperidine heterocycle is a privileged motif that appears in countless bioactive molecules, including natural products and drugs. As the most prevalent nitrogen-containing heterocycle in chemical therapeutics, the piperidine motif is featured in a plethora of blockbuster drugs. Due to the prevalence of piperidines, new and innovative methodologies to access this motif remain highly sought after. Strained alkyne intermediates such as benzyne and piperidyne have proven to be useful intermediates towards this end, however cycloadditions to these scaffolds typically lead to the introduction of sp2 centers. The use of highly reactive cyclic allenes introduces an added layer of complexity by building an sp3 center and vicinal stereocenters. The proposed research aims to develop the first 3,4-azacyclohexylallne Diels-Alder reaction capable of accessing decorated piperidines that possess quaternary centers. This new strategy will then be employed to complete a concise total synthesis of the manzamine alkaloid Acantholactone.

项目摘要/摘要哌啶杂环是一种特权基序，出现在无数的生物活性分子中，包括天然产品和药物。作为化学疗法中最普遍的含氮的杂环，哌啶基序在大量的大片药物中出现。由于哌啶的流行，新的和访问此主题的创新方法仍在备受追捧。紧张的炔烃中间体，例如 Benzyne和Piperidyne已被证明是针对此目的的有用中间人这些脚手架通常会导致SP2中心的引入。引入高反应性循环艾伦的使用通过构建SP3中心和替代立体中心的添加复杂性层。拟议的研究目的开发第一个3,4-氮杂己糖allne-alder-alder-alder反应，能够访问装饰的哌啶拥有第四纪中心。然后，将采用这种新策略来完成简洁的总合成曼氮胺生物碱腺苷。