SYNTHESIS OF BIOLOGICALLY ACTIVE NATURAL PRODUCTS

生物活性天然产物的合成

• 批准号: 3279312
• 负责人: MICHAEL E JUNG
• 金额: $ 7.56万
• 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 1985-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3279312
• 关键词: Diels Alder reaction; alkaloids; codeine; cortisone; drug design /synthesis /production; estrone; lignans; morphine; 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 pentacyclic alkaloids (morphine, codeine, reserpine, and herquline) and tetracyclic steriods (cortisone, estrone) and bionans (desmethyl epipodophyllotoxin) to the simple bicyclic alkaloid slaframine. The key step of all of the synthetic approaches is an intramolecular reaction or rearrangement which requires, by the intramolecularity of the process, the formation of the stereochemically desired isomer in preference to all others. The intramolecular processes used in these syntheses are Diels-Alder reations, [3,3]-sigmatropic shifts, and nucleophilic additions (Michael additions or additions to immonium salts). In all cases, the syntheses are designed so as to be quite short (9 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 synthese - e.g., formation of quaternary centers via an oxy-Cope rearrangement, steric control of the stereochemistry of internal cycloadditions, the facile generation and cyclization of 1-azabutadienes, 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 chemistry 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 从复杂的五边形生物碱（吗啡，可待因，治疗和 Herquline）和四环素固有（可的松，雌酮）和Bionans （脱甲基附生噬蛋白）到简单的双环生物碱slaframine。 所有合成方法的关键步骤是分子内 反应或重排需要，通过分子内分子 过程，在偏爱中形成立体化学所需的异构体 向其他所有人。 这些合成中使用的分子内过程是 DIELS-ALDER REATIONS，[3,3] - 含量偏移和亲核添加 （迈克尔盐添加或添加给原子盐）。 在所有情况下， 合成的设计以使其很短（吗啡9步，7个步骤 雌狮等的步骤）和足够的一般，以至于许多其他结构上 相关系统可以很容易地形成。 在 这些合成 - 例如，通过氧气形成了第四纪中心 重排，内部立体化学的空间控制 环加成，1-扎布丁的轻松生成和环化， 除其他外，将是适用的，并且非常有机合成 一般来说。 由于合成的极端短缺， 目标的重要性和方法的高内在价值 他们自己，对化学做出重要贡献的可能性是 很高。