ACYCLIC STEREOSELECTION IN NATURAL PRODUCT SYNTHESIS

描述：（逐字从申请人的摘要）计划是 完成了spongistatin 1（altohrytin）的全合成 A），一种海洋来源的强效抗真菌和细胞毒性剂。因为 由于其强大的生物活性，海绵抑素是一种有前途的候选药物， 但实际上不可能获得足够的数量 从天然来源。这个项目的目标是开发一个综合的 这是足够实用的，它可以用来制备 大约5克的材料，这将足以 一期临床试验 还提出了计划，以完成14个- 大环内酯类抗生素兰卡霉素。虽然是一个高效的， 开发了一条合成苷元开环酸的简便路线 在以前的工作中，大环内酯化反应尚未被 办妥了一批事实上，这种常见的转变往往是一个限制步骤 在大环内酯全合成中。下一个项目期的目标是 应用现代计算机建模方法，NMR构象 分析和合成，以鉴定用于该方法的合适底物。 大环内酯化

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.