THE TOTAL SYNTHESIS OF AXINELLAMINE A

axinellamine A 的全合成

• 批准号: 6070464
• 负责人: JEFFREY A SCHULTZ
• 金额: $ 3.09万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-10 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6070464
• 关键词: Diels Alder reaction; alkaloids; antineoplastics; biological products; cyclization; drug design /synthesis /production; heterocyclic polycyclic compound; molecular shape; stereochemistry; ylide

DESCRIPTION The object of this proposal is the total synthesis of axinellamine A, a member of a class of compounds that has shown anti-cancer activity. The synthesis is based around using a key intramolecular [3+2] azomethine ylide cyclization to form the very densely functionalized octahydro cyclopenta pyrole core. Some of the difficult problems in the synthesis to be addressed include the five stereogenic centers on the one ring, two guanidine rings and the introduction of two dibromopyrrole carboxylamides. The goals of this proposal will include: 1) Synthesis of a cyclization substrate based on a asymmetric Diels-Alder reaction 2) Studying the key issues of the azomethine ylide cyclization, which are the reactivity of the dipolarophile, the generation and reactivity of the dipole, and the stereochemistry of the cyclization. 3) Synthesis of the final product and 4) Determination of the absolute configuration of the molecule. The synthesis of this molecule would be an important contribution to a growing class of natural products.

描述 本提案的目的是全合成 axinellamine A，它是一类已显示出抗癌活性的化合物的成员。该合成基于使用关键的分子内[3+2]偶氮甲碱叶立德环化来形成非常致密的功能化八氢环戊吡咯核心。合成中需要解决的一些难题包括一个环上的五个立体中心、两个胍环以及两个二溴吡咯甲酰胺的引入。该提案的目标包括：1）基于不对称Diels-Alder反应合成环化底物2）研究偶氮甲碱叶立德环化的关键问题，即亲偶极试剂的反应性、偶极子的产生和反应性，以及环化的立体化学。 3) 最终产物的合成和4) 分子绝对构型的测定。该分子的合成将为不断增长的天然产物类别做出重要贡献。