SYNTHESES OF BIOLOGICALLY ACTIVE NATURAL PRODUCTS

生物活性天然产品的合成

• 批准号: 3279308
• 负责人: MICHAEL E JUNG
• 金额: $ 14.02万
• 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/3279308
• 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的方法， 全合成多种具有药用活性的天然产物。 靶分子在其结构复杂性方面差异很大， 从复杂的多环生物碱（吗啡，可待因，利血平， 哌嗪霉素，deosybouvardin和herquline和萜烯（可的松， 雌酮，plaunol C，ajugarins）和木脂素（去甲基表鬼臼毒素） 大环虫菌素。 几乎所有合成的关键步骤 方法是分子内反应或重排， 通过这个过程的分子内性， 立体化学所需异构体优先于所有其它异构体。 的 在这些合成中使用的分子内方法是Diels-Alder反应， （3，3）-正负号位移和亲核加成（迈克尔加成或 添加到亚铵盐中）。 在所有情况下，合成被设计为 因为是相当短的（8个步骤吗啡，7个步骤雌酮，等等）和 足够普遍，因此许多其他结构相关的系统可以 很容易形成。 在这些合成中开发的原理-例如， 通过符号迁移重排形成四元中心，空间 内环加成立体化学的控制，新的保护 氨基酸序列，除其他外-将是适用的， 对有机合成有重要意义。 由于极端短暂的 目标的综合性、重要性和高内在价值 的方法本身，一个重要的贡献， 血流量相当高。