ACYCLIC STEREOSELECTION IN NATURAL PRODUCT SYNTHESIS

描述：(逐字摘自申请者摘要)图则为 提出完成海绵抑素1(Altohrytin)的全合成 A)，海洋来源的一种有效的抗真菌和细胞毒剂。因为 海绵抑素具有强大的生物活性，是一种很有前途的候选药物， 但几乎不可能获得足够的数量 来自自然资源。这个项目的目标是开发一种综合 这是非常实用的，可以用来准备 大约5克的材料，这将足以 一期临床试验。 还提出了完成14个化合物的总合成的计划- 成员大环内酯类抗生素兰卡霉素。虽然这是一个高效和 开发了一条合成苷元二酸的简便路线。 在以前的工作中，大内酯反应还没有被 已实现。事实上，这种常见的转换通常是一个限制步骤 在大环内酯全合成中。下一个项目期的目标是 应用现代计算机模拟方法，核磁共振构象 分析和合成以确定适合该酶的底物 大内酯化。

DESCRIPTION: (Verbatim from the Applicant's Abstract) Plans are presented to complete a total synthesis of spongistatin 1 (altohrytin A), a potent antifungal and cytotoxic agent of marine origin. Because of its potent bioactivity, spongistatin is a promising drug candidate, but it would be virtually impossible to obtain sufficient quantities from natural sources. The goal of this project is to develop a synthesis that is sufficiently practical that it can be used to prepare approximately five grams of the material, which would be sufficient for a phase I clinical trial. Plans are also presented to complete a total synthesis of the 14- membered macrolide antibiotic lankamycin. Although an efficient and convenient synthetic route to the aglycone seco-acid has been developed in previous work, the macrolactonization reaction has not yet been achieved. In fact, this common transformation is often a limiting step in macrolide total synthesis. The goal of the coming project period is to apply modern methods of computer modelling, NMR conformational analysis, and synthesis to identify a suitable substrate for the macrolactonization.