TOTAL SYNTHESIS OF THE CYTOTOXIC MACROLIDE FORMAMICIN

细胞毒性大环内酯福马霉素的全合成

• 批准号: 6179839
• 负责人: NOEL A POWELL
• 金额: $ 0.91万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6179839
• 关键词: antifungal antibiotics; drug design /synthesis /production; macrolide antibiotics

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.

提出的研究计划的目标是开发合成甲氨基霉素，一种新的细胞毒性抗真菌抗生素。formamicin是抗生素hygrolide家族的一员，在体外对几种白血病细胞系显示出非常强的细胞毒性（1C50 = 0.13- 0.15 ng/mL）。甲虫霉素的结构对有机化学家提出了几个合成挑战。提出的合成是高度收敛的，并展示了一种新的方法来形成2,6-二脱氧- β -糖苷。此外，我们希望提出一种新的手性-烷氧烯基锡烷在醛上的添加，以在一个步骤中形成不同保护的抗1,2-丙炔二醇。