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Method and Strategy Development for the Synthesis of Physiologically Important Natural Products

合成具有生理重要性的天然产物的方法和策略开发

基本信息

批准号：
10580775
负责人：
JOHN L WOOD
金额：
$ 29.78万
依托单位：
BAYLOR UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10580775
关键词：
Acids Aldehydes Alkaloids Alkynes Anti-Inflammatory Agents Antibiotics Antifungal Agents Architecture Area Benign Biological Biomedical Research Bromides Cancer cell line Carbon Chemistry Collaborations Collection Complex Coupling Development Elements Endowment Environment FDA approved Grant Hand Health Hepatitis C virus Human Hydrogenation Hydroxamic Acids In Situ Investigation Ketones Laboratories Lead Learning Medicine Methodology Methods Molecular Natural Products Nature Nitrogen Oxidants Oxygen Pharmaceutical Preparations Physiological Postdoctoral Fellow Preparation Production Property Protocols documentation Reaction Research Personnel Resolution Route Science Securinega Solvents Structure-Activity Relationship Synthesis Chemistry System Techniques Technology Terpenes Therapeutic United States National Institutes of Health Viral Work anti-cancer cyclic ketone cycloaddition cytotoxicity diketopiperazine drug development drug-like compound falls functional group graduate student member natural product derivative novel novel therapeutics research and development scaffold screening skills

项目摘要

PROJECT SUMMARY/ABSTRACT Over the past three decades, 28% of all new FDA approved drugs have been natural products, or derived from natural products, while 27% have been entirely synthetic in origin. Thus, the pursuit of new synthetic methods and strategies to access complex molecules is not only a worthy pursuit, but a critical component of biomedical research and drug development that also contributes novel elements of synthetic strategy and methods to the lexicon of synthetic chemistry. The studies proposed within this application describe the pursuit of six different natural products that fall into three general classes (diketopiperazine, alkaloid, and terpenoid). These compounds possess a range of biological activities including: leishmanicidal, NO production inhibition, anti- inflamatory, antiinsectan, antifungal, antiviral, cytotoxicity against a variety of cancer cell lines, as well as anti- proliferative activity. For the diketopiperazine and alkaloid projects we are aiming to develop ring expansion technology that will enable efficient access to imbedded hydroxamic acid intermediates. More specifically: Aim 1, entails syntheses of the N-hydroxy-2,5-diketopiperazine-derived (NHDKP) natural products haenamindole, raistrickindole A, and 14-hydroxyterezine D. This aim also includes the development of a regioselective ring expansion of tetramic acids that will enable the direct acces of to highly functionalized NHDKP’s. Aim 2 focuses on syntheses of phyllantidine and flueggeacosine B, two members of a securinega alkaloid subset that contain N-O bonds. The scope of the optimized ring-expansion chemistry developed in Aim-1 will be expand in this aim to deliver key intermediates in both syntheses. Aim 3 is a departure from aims 1 and 2 and turns toward further development of keteniminium chemistry by its application in a complex synthetic setting. At present, work toward each aim is at a different stage of development and this development will continue to evolve over the course of the grant period. As with all of our synthetic endeavors, collections of intermediates will be submitted to the NIH for SAR studies and once materials are in hand further collaborations are sought. In addition to direct contributions to biomedical science afforded by the latter, our synthetic efforts have (and will continue to) educate graduate students and postdoctoral researchers in the planning and execution of complex molecule synthesis.

项目总结/文摘

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Staurosporine Analogs Via C–H Borylation

通过 C–H 硼化获得星形孢菌素类似物

DOI：
10.1021/acsmedchemlett.0c00420
发表时间：
2020
期刊：
ACS Medicinal Chemistry Letters
影响因子：
4.2
作者：
Gayler, Kevin M.;Kong, Ke;Reisenauer, Keighley;Taube, Joseph H.;Wood, John L.
通讯作者：
Wood, John L.