STRATEGIES FOR THE SYNTHESIS OF BIOACTIVE TARGETS

描述：本文概述的研究计划是针对 设计和开发新的一般策略， 天然和非天然产品，具有显著的生物活性， 活动 在这些调查过程中， 所选反应和工艺的局限性将在 复杂分子全合成的背景和新方法 用于碳-碳键形成和官能团操作的是 等待被发现 注意到具体的综合目标包括完成 几种重要的生物天然产物的全合成 包括抗真菌抗生素安替星和大环内酯 抗生素红霉素B。综合的基本策略 这些化合物中的每一种都是会聚的， 由其衍生的呋喃和氢吡喃的加工。新方法和 用于不对称合成1，2，3-三取代 环丙烷和用于立体选择性构建三取代的 开发和应用烯烃。据悉该 红霉素B的制备方法是独特的， 糖基化的开环酸衍生物。主要研究者 表明携带红霉素的简单类似物 简化分子框架上的关键碳水化合物残基将 设计和制备，以阐明红霉素 药效团并最终鉴定新型的口服活性物质 抗生素他进一步指出，一些新的生物活性， 已经选定了目标，将作为论坛， 新化学发明，并指出实例， FR 900482的合成，一种与肿瘤相关的有效抗癌候选物， 将使用具有临床活性的丝裂霉素。他说，钥匙 这是他合成这种有趣的生物碱的策略之一 需要烯烃复分解反应来构建高度 官能化的氮杂环。据悉，一份简明 一种新的角鲨烯合成酶抑制剂萨拉戈萨酸A的研究方法， 设计了一种乙烯基羟醛反应来组装 构成双环核心结构的碳。 应注意，天然产物和所选产物的量 将准备向C. P. Starks，Inc.提交同系物，伊莱 礼来公司、默克公司、雅培实验室和葛兰素公司的生物 作为潜在抗生素和抗真菌剂的评价， 降胆固醇剂和抗癌剂。

DESCRIPTION: The research program outlined herein is directed toward the design and development of novel general strategies for the syntheses of natural and unnatural products that possess significant biological activity. During the course of these investigations, the scope and limitations of selected reactions and processes are to be explored in the context of the total synthesis of complex molecules, and new methods for carbon-carbon bond formation and functional group manipulation are to be discovered. It is noted that the specific synthetic objectives include completion of the total syntheses of several biologically important natural products including the antifungal antibiotic ambruticin and the macrolide antibiotic erythromycin B. The basic strategies for the syntheses of each of these compounds are convergent and involve the stereoselective elaboration of furans and hydropyrans derived therefrom. New methods and catalysts for the asymmetric synthesis of 1,2,3-trisubstituted cyclopropanes and for the stereoselective construction of trisubstituted olefins are to be developed and applied. It is reported that the approach to erythromycin B is unique and involves the macrolactonization of a glycosylated seco-acid derivative. The principal investigator indicates that simple analogues of the erythromycins that bear the critical carbohydrate residues on a simplified molecular framework will be designed and prepared in an effort to elucidate the erythromycin pharmacophore and ultimately to identify novel, orally-active antibiotics. He further notes that several new biologically active targets have been selected that will serve as the forum for the invention of new chemistry and indicates that example that the total synthesis of FR900482, a potent anticancer candidate related to the clinically active mitomycins will be undertaken. He states that the key element of his strategy for the synthesis of this intriguing alkaloid entails an olefin metathesis reaction to construct a highly functionalized nitrogen heterocycle. It is reported that a concise approach to zaragozic acid A, a novel squalene synthase inhibitor, has been devised that features a vinylogous aldol reaction to assemble the carbons constituting the bicyclic core structure. It is noted that quantities of the natural products and selected congeners will be prepared for submission to C.P. Starks, Inc., Eli Lilly Company, Merck, Abbott Laboratories, and Glaxo for biological evaluation as potential antibiotics and as antifungal, hypocholesterolemic and anticancer agents.