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.

该建议旨在开发和测试几种新方法 多种药物活性天然产品的总合成。 靶分子的结构复杂性差异很大，范围很大 从复杂的多环生物碱（吗啡，可待因，治疗， 哌嗪霉素，脱氧核心和赫尔克林和萜烯 雌酮，plaunol C，ajugarins）和木糖（desmethyl epodophodyllotoxin） 到大环蛋白。 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，形成了 立体化学希望异构体优先考虑。 这 这些合成中使用的分子内过程是Diels-Alder反应， （3,3） - 签名移动和亲核的添加（迈克尔添加或 盐盐的添加）。 在所有情况下，综合都设计了 为了很短（到吗啡的8个步骤，7个步骤的雌酮等）和 足够一般，以至于许多其他与结构相关的系统可能是 很容易形成。 这些合成中发展的原理 - 例如， 通过标志性重排的Quaternery中心形成中心 控制内部环加成的立体化学，新保护 氨基酸的序列等是适用的，并且很棒 总体上对有机合成的价值。 由于极端短缺 综合，目标的重要性和高内在价值 这些方法本身，重要的可能性 Dhemistry很高。