SYNTHESIS OF THE (3.1.1)BICYCLIC RING SYSTEM OF TXA2

TXA2 (3.1.1)双环体系的合成

• 批准号: 3341886
• 负责人: Robert Michael Williams
• 金额: $ 6.25万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-07-01 至 1986-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3341886
• 关键词: acetylation; arachidonate; bicyclic compound; drug design /synthesis /production; hydrolysis; platelets; polymers; pyrans; thromboxanes; vasoconstriction; vasodilators

The objective of the proposed research is to develop a unique and mild synthetic technique to construct the labile [3.1.1.] bicyclic acetal ring system found in thromboxane A2 (TXA2). Thromboxane A2 is an unstable (t1/2 30-40 s at 37C) major metabolite of the arachadonic acid cascade in human platelets with potent thrombotic and vasoconstricting properties; the structure proposed has not been rigorously verified. This proposal outlines a mild and practical method for the overall dehydrative ring closure of 1,3-dihydroxypyronosides to the corresponding bicyclic [3.1.1.] acetals using polymer-supported reagents. In this way, the labile products can be cleanly recovered from the polymer-bound reaction by-products without a chromatographic separation. The present methodology is readily adaptable to the conversion of TXB2 (the stable hydrolysis product of TXA2) into TXA2. This shall provide a non-aqueous preparation of TXA2 for structure determination and that of simpler analogs for biological investigation.

提出的研究目的是开发一种独特的和温和的