SYNTHESES OF BIOLOGICALLY ACTIVE NATURAL PRODUCTS

生物活性天然产品的合成

• 批准号: 3279314
• 负责人: MICHAEL E JUNG
• 金额: $ 13.59万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-01-01 至 1990-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3279314
• 关键词: Diels Alder reaction; alkaloids; codeine; cortisone; drug design /synthesis /production; estrone; lignans; morphine; podophyllin; reserpine; stereochemistry; steroids

This proposal is designed to develop and test several new approaches to the total synthesis of a wide variety of medicinally active natural products. The target molecules vary greatly in their structural complexity, ranging from the complex polycyclic alkaloids (morphine, codeine, reserpine, piperazinomycin, deosybouvardin and herquline and terpenes (cortisone, estrone, plaunol C, ajugarins) and lignans (desmethyl epipodophyllotoxin) to the macrocycle invermectin. The key step of nearly all of the synthetic approaches is an intramolecular reaction or rearrangement which requires, by the intramolecularity of the process, the formation of the stereochemistry desired isomer in preference to all others. The intramolecular processes used in these syntheses are Diels-Alder reactions, (3,3)-signatropic shifts, and nucleophilic additions (Michael additions or additions to immonium salts). In all cases, the syntheses are designed so as to be quite short (8 steps to morphine, 7 steps to estrone, etc.) and general enough so that many other structurally related systems could be formed quite easily. The principles developed in these syntheses - e.g., formation of quaternery centers via signmatropic rearrangements, steric control of the stereochemistry of internal cycloadditions, new protection sequence for amino acids, among others - would be applicable and of great value to organic synthesis in general. Because of the extreme shortness of the syntheses, the importance of the targets, and the high intrinsic value of the methods themselves, the likelihood of an important contribution to dhemistry is quite high.

该提案旨在开发和测试几种新方法 多种具有药用活性的天然产物的全合成。 目标分子的结构复杂性差异很大，范围 来自复杂的多环生物碱（吗啡、可待因、利血平、 哌嗪霉素、deosybouvardin 和赫奎林以及萜烯（可的松、 雌酮、普劳诺尔 C、金缕梅素）和木脂素（去甲基表鬼臼毒素） 为大环阿维菌素。 几乎所有合成的关键步骤 方法是分子内反应或重排，需要， 通过该过程的分子内性，形成 立体化学所需的异构体优先于所有其他异构体。 这 这些合成中使用的分子内过程是狄尔斯-阿尔德反应， (3,3)-签名位移和亲核加成（迈克尔加成或 添加到亚铵盐中）。 在所有情况下，合成的设计都是如此 相当短（吗啡 8 个步骤，雌酮 7 个步骤等）并且 足够通用，以至于许多其他结构相关的系统可以 很容易形成。 这些合成中开发的原理 - 例如， 通过符号重排、空间位阻形成四元中心 控制内环加成的立体化学，新的保护 氨基酸序列等 - 将是适用的并且具有重要意义 对一般有机合成的价值。 由于极度短缺 综合、目标的重要性以及高内在价值 方法本身的重要贡献的可能性 dhemistry 相当高。