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Synthesis of Biologically Active Terpenoids

生物活性萜类化合物的合成

基本信息

批准号：
10587602
负责人：
David Sarlah
金额：
$ 37.1万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-02-01 至 2027-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10587602
关键词：
Acceleration Adverse effects Affect Anti-Infective Agents Antineoplastic Agents Architecture Biological Biological Testing Biology Breathing Cancer cell line Cessation of life Chemical Engineering Chemical Structure Chemicals Chemistry Collaborations Communicable Diseases Complex Creativeness Cyclization Development Disease Evaluation Excision Goals Human Indenes Investigation Isomerism Knowledge Lead Malignant Neoplasms Medicine Metabolic Metastatic/Recurrent Methodology Methods Molecular Molecular Mechanisms of Action Molecular Probes Molecular Target Mutation Natural Products Nature Neoplasm Metastasis Oncogenes Oncology Operative Surgical Procedures Organic Synthesis Organism Outcome Pathogenicity Patients Periodicity Pharmaceutical Chemistry Pharmaceutical Preparations Pharmacologic Substance Polyenes Preparation Primary Neoplasm Prodrugs Property Radiation therapy Rationalization Reactive Inhibition Research Resistance Role Signal Pathway Signal Transduction Source Specificity Stereoisomer Structure Terpenes Testing Therapeutic Toxic effect Toxicology Work analog anti-cancer anticancer activity bioactive natural products cancer therapy carcinogenicity chemical synthesis clinical development cytotoxic driving force drug development effective therapy fighting flexibility infectious disease treatment metabolic profile molecular targeted therapies natural product inspired novel novel strategies pathogen prevent programs scaffold small molecule standard of care tool tumor

项目摘要

PROJECT SUMMARY Natural products continue to be one of the most important sources of new lead compounds for the discovery of medicinal agents. They occupy vast regions of chemical space, providing much greater diversity in their structures as well as their biological properties compared to those of classical drug molecules. Potent compounds from nature have provided paramount architectural inspiration for developing new chemical therapies, with more than 80% of all drugs and over 65% of anticancer drugs being, derived from, or inspired by natural products; however, their structural complexity and limited availability are often the sole obstacles preventing their further study and clinical development. As synthetic organic chemists situated at the interface of chemistry and biology, our research program is devoted to providing solutions to this supply problem in the form of sustainable and practical syntheses of complex biologically active natural products, and to performing fundamental studies of their chemical biology. By developing new synthetic strategies, as well as target-specific methodologies, we intend to provide efficient access to complex bioactive natural products and bring them within the realm of medicinal chemistry. Specifically, in this proposal we describe synthetic approaches to several diverse terpenoid natural product classes: isomalabaricane triterpenoids, nimbolide, and a vast range of perhydrobenz[e]indene-based terpenoids. We already established stereodivergent access to all four challenging stereoisomers of the rare 6/6/5 tricyclic terpenoid core structure that occurs in nature. Moreover, we recently completed several isomalabaricanes, using synthetic blueprint that permits rapid diversification. We are beginning to engage in biological investigations, and our ongoing collaboration with chemical biology experts will provide an excellent opportunity to test these compounds and their analogues for therapeutic activities, as well as to elucidate their mechanisms of action, molecular targets, and metabolites. It is expected that these studies will provide anticancer and anti-infective agents with unprecedented molecular topologies and functions, as well as advance our basic knowledge of their mechanistic specificity for certain cancers and pathogenic diseases.

项目总结