ACYCLIC STEREOSELECTION IN NATURAL PRODUCT SYNTHESIS

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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.