TOTAL SYNTHESIS OF THE CYTOTOXIC MACROLIDE FORMAMICIN

提出的研究计划的目标是开发一种新型的细胞毒性抗真菌抗菌药物甲氧米星的合成。作为湿润内酯类抗生素家族的一员，福拉米星在体外对几种白血病细胞株表现出很强的细胞毒活性(1C50=0.13-0.15 ng/mL)。甲氧米星的结构对有机化学家提出了几个合成挑战。建议的合成是高度收敛的，并展示了一种新开发的形成2，6-二脱氧-β-糖苷的方法。此外，我们还希望提出一种新的方法，将手性伽马-烷氧基烯丙基锡烷加成到醛上，一步得到不同保护的抗1，2-丙叉二醇。

The goal of the proposed research plan is the develop a synthesis of formamicin, a novel cytotoxic antifungal antiobiotic. A member of the hygrolide family of antibiotics, formamicin exhibits very potent in vitro cytotoxicities towards several leukemia cell lines (1C50 = 0.13- 0.15 ng/mL). The structure of formamicin presents several synthetic challenges to the organic chemist. The proposed synthesis is highly convergent and showcases a newly developed method for the formation of 2,6-dideoxy-beta-glycosides. In addition, we wish to propose a novel addition of chiral gamma-alkoxyallenyl stannanes to aldehydes to form differently protected anti-1,2-propargylic diols in a single step.