Chemical Synthesis of Complex Natural Products for Translational Science

用于转化科学的复杂天然产物的化学合成

基本信息

批准号：
9920757
负责人：
JOHN A PORCO
金额：
$ 66.79万
依托单位：
BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-01 至 2021-04-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The goals of the proposed MIRA (R35) research program are to continue chemical syntheses of bioactive molecules and expand our efforts and capabilities in translational science. The MIRA effort will allow flexibility and stability to enabe important new research directions that come up during the course of research. Our two NIGMS-funded RO1 grants (Biomimetic Synthesis of Complex Natural Products (GM-073855) and Chemical Synthesis of Bioactive Flavonoid and Xanthone-Derived Natural Products) have been highly productive and have led to 41 publications from 2015 - 2010. These include 19 collaborative manuscripts with clinical and biological investigators. As part of our studies, we have taken opportunities to address key questions and contemporary needs in organic chemistry including asymmetric catalysis of photocycloadditions, enantioselective dearomatization, and atropselective synthesis. Key accomplishments in the past five years include asymmetric photocycloadditions of 3-hydroxyflavones to access rocaglate antitumor agents, synthesis of derivatives of the tubulin inhibitor chamaecypanone C using copper-mediated enantioselective oxidative dearomatization, synthesis of the anticancer agents and antibiotics kibdelones A and C using Pt(IV)-mediated arylations of quinone monoketals, and synthesis of the antibiotic rugulotrosin A employing vinylogous addition of siloxyfurans to chromones and atropselective dimerization. As part of the proposed MIRA project, the Principal Investigator Professor John Porco and colleagues will continue development of novel synthetic methodologies for concise entry to bioactive classes of natural products including oxaphenalenones, meroterpenoids, polyprenylated acylphloroglucinols, tetrahydroxanthones, and dimeric chromones. The project will continue major emphasis on collaborations to study biological properties and mode of action (MoA) of target molecules for ultimate use as pharmacological therapies for human cancers as well as viral and bacterial illnesses. It is anticipated that the MIRA effort will allow us to continue development of innovative syntheses of complex natural products and derivatives and continue work to highly interface these studies with applications of compounds in clinical and translational research.

描述（由适用提供）：拟议的MIRA（R35）研究计划的目标是继续生物活性分子的化学合成，并扩大我们在转化科学领域的努力和能力。 MIRA的努力将允许灵活性和稳定性，以实现在研究过程中出现的重要新研究方向。我们的两个NIGMS资助的RO1赠款（复杂天然产物的仿生合成（GM-073855）和生物活性类黄酮和Xanthone衍生的天然产物的化学合成）具有很高的生产力，并且已导致2015年至2010年的41个出版物。这些是从2015年到2010年的出版物。其中包括19种与临床和临床研究人员的协作手册。作为我们研究的一部分，我们借此机会解决了有机化学方面的关键问题和当代需求，包括对光细胞载体的不对称催化，对映选择性的亲爱的疗法和萎缩性合成。在过去五年中的主要成就包括3-羟基氟烷的不对称光载体，以访问Rocaglate抗肿瘤剂，使用铜介导的抗氧化抗氧化抗体和抗生素kib，Chamaecanone C的衍生物合成微管蛋白抑制剂Chamaecypanone C的衍生物pt（iv）介导的喹酮单因子的芳基，以及抗生素浓蛋白蛋白的合成A使用硅氧基呋喃添加到染色体和萎缩性二聚化中。作为拟议的MIRA项目的一部分，首席研究员John Porco教授及其同事将继续开发新型的合成方法，以简化天然产品的生物活性类别，包括氧甲烯酮，甲基苯甲酸酯，多丙基化的酰基化酰基氯酸氨基醇，四氢烷基二烷基二烷基氨基烷基和斑点Chromones。该项目将继续重视研究目标分子的生物学特性和作用方式（MOA），以最终用作人类癌症以及病毒和细菌疾病的药物疗法。预计MIRA的努力将使我们能够继续开发复杂天然产品和衍生物的创新合成，并继续致力于在临床和转化研究中的化合物应用中高度接触这些研究。