NEW STRATEGIES FOR GLYCOCONJUGATE SYNTHESIS FROM ALKYNES

从炔烃合成糖复合物的新策略

基本信息

批准号：
2837673
负责人：
Frank Edward McDonald
金额：
$ 11.68万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-04-07 至 1999-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2837673
关键词：
alkynes antiAIDS agent antifungal agents antineoplastic antibiotics carbohydrates chemical conjugate chemical synthesis cyclization drug design /synthesis /production glycosides isomer molybdenum nucleosides rhodium

项目摘要

This proposal describes new reactions and methods for the chemical synthesis of two general families of biologically significant glycoconjugates: (1) furanosyl and pyranosyl nucleosides, and (2) C- arylglycosides. The long term objectives are to develop new transition metal-mediated reactions for the efficient preparation of antitumor and antiviral carbohydrate-containing compounds. This proposal describes our continued work with molybdenum pentacarbonyl- mediated cycloisomerization reactions of alkynyl alcohols to endocyclic enol ethers (glycals) and specific application of this chemistry to anti- AIDS nucleosides such as dideoxynucleosides, the antineoplastic compound puromycin, and antifungal compounds such as polyoxin and amipurimycin. Our efforts will focus on extending the scope of the cycloisomerization to amide-containing alkynols, as well as extension to pyranosyl nucleosides. We will also study new postcyclization strategies for preparing nucleosides from glycals. This application also features the rhodium-catalyzed cyclotrimerization of alkynyl-carbohydrates. We propose application of this methodology to a short, direct synthesis of the antifungal drug papulacandin, as well as extending this approach to the angucycline antitumor antibiotic urdamycinone. We will also explore this methodology for the synthesis of C-arylglycoside compounds which have not yet been synthesized, such as ravidomycin as well as the bis-C-aryl glycoside, kidamycin.

该提案描述了化学物质的新反应和方法两个一般具有生物学意义的一般家族的合成糖缀合物：（1）呋喃糖基和吡喃糖基核苷，以及（2）c- 芳基糖苷。长期目标是发展新的过渡金属介导的反应有效制备抗肿瘤和含碳水化合物的化合物。该提案描述了我们继续与戊巴略还是藻类酒精对内吞醇的介导的环异构反应烯醇醚（Glycals）和该化学的特定应用艾滋病核苷，例如二乙氧基核苷，抗肿瘤化合物嘌呤霉素和抗真菌化合物，例如多氧和阿硫咪霉素。我们的努力将着重于将环化组体的范围扩展到含有酰胺的藻醇，以及向吡喃糖基核苷延伸。我们还将研究准备新的循环后策略来自糖的核苷。该应用程序还具有阳极催化的环三聚体藻类碳水化合物。我们建议将此方法应用于短而直接合成抗真菌药物丘疹蛋白以及将这种方法扩展到angucycline抗肿瘤抗生素乌达米酮。我们还将探讨这种合成的方法尚未合成的C-芳基糖苷化合物，例如 Ravidyomycin以及Bis-C-芳基糖苷Kidamycin。