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: 6013425
• 负责人: NOEL A POWELL
• 金额: $ 3.03万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6013425
• 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.

本课题的研究目标是合成一种新型的细胞毒性抗真菌抗生素--福霉素。甲霉素是环内酯抗生素家族的成员，对多种白血病细胞系表现出非常强的体外细胞毒性（1C 50 = 0.13- 0.15 ng/mL）。 甲酸霉素的结构对有机化学家提出了几个合成挑战。所提出的合成是高度收敛的，并展示了一种新开发的方法，用于形成2，6-双脱氧-β-糖苷。此外，我们希望提出一种新的除了手性γ-烷氧基丙二烯基锡烷醛形成不同的保护反-1，2-炔丙基二醇在一个单一的步骤。