R35GM141963

Development of New Strategies for Chemical Synthesis and Study of Complex Natural Products - Project Summary/Abstract

The detailed study of the fundamental chemistry and biological properties of complex natural products provides critical insight toward understanding their mode of action and enables the development of new approaches for the treatment of various human ailments.

This research program focuses on the development of efficient and concise strategies for the total chemical syntheses of structurally complex and biologically active natural products. The target compounds are selected based on the novelty of molecular architecture and associated challenges, paucity of prior synthetic studies, abundance of opportunities for the development of new synthetic strategies and methodologies, possession of significant biological activity, and the potential for future chemical and biological studies.

The systematic discovery, development, and application of new synthetic strategies and methodologies explored in this program continue to provide synthetic samples of rare and precious compounds for structure validation and detailed examination of their chemistry and biology.

This program focuses on synthetic studies of the rich families of complex natural products including cyclotryptamine, diketopiperazine, and monoterpene indole alkaloids. A central interest is the development of generalizable directed, regioselective, stereoselective, and efficient union of complex fragments providing late-stage couplings to secure challenging linkages, including complete stereocontrol at quaternary stereogenic centers.

Convergent and guided assembly of advanced fragments is complemented by the development and application of new highly selective chemical transformations for the rapid generation of molecular complexity. These transformations include new methods for amide derivatization, azaheterocycle syntheses, cascade bond-forming reactions involving enamines, stereoretentive hydroxylation of complex substrates, and stereocontrolled sulfidation made possible through employing new reagents and conditions developed in this program.

This program's access to a potent collection of families of complex alkaloids and related derivatives continues to enable exciting biochemical collaborative investigations. The array of synthetic molecules accessed through this program holds great promise as new bioactive compounds and mechanistic tools, and these compounds are continually evaluated and examined through multidisciplinary collaborations.

Massachusetts Institute Of Technology

THE NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES (NIGMS) SUPPORTS BASIC RESEARCH THAT INCREASES OUR UNDERSTANDING OF BIOLOGICAL PROCESSES AND LAYS THE FOUNDATION FOR ADVANCES IN DISEASE DIAGNOSIS, TREATMENT, AND PREVENTION. NIGMS ALSO SUPPORTS RESEARCH IN SPECIFIC CLINICAL AREAS THAT AFFECT MULTIPLE ORGAN SYSTEMS: ANESTHESIOLOGY AND PERI-OPERATIVE PAIN, CLINICAL PHARMACOLOGY ?COMMON TO MULTIPLE DRUGS AND TREATMENTS, AND INJURY, CRITICAL ILLNESS, SEPSIS, AND WOUND HEALING.? NIGMS-FUNDED SCIENTISTS INVESTIGATE HOW LIVING SYSTEMS WORK AT A RANGE OF LEVELSFROM MOLECULES AND CELLS TO TISSUES AND ORGANSIN RESEARCH ORGANISMS, HUMANS, AND POPULATIONS. ADDITIONALLY, TO ENSURE THE VITALITY AND CONTINUED PRODUCTIVITY OF THE RESEARCH ENTERPRISE, NIGMS PROVIDES LEADERSHIP IN SUPPORTING THE TRAINING OF THE NEXT GENERATION OF SCIENTISTS, ENHANCING THE DIVERSITY OF THE SCIENTIFIC WORKFORCE, AND DEVELOPING RESEARCH CAPACITY THROUGHOUT THE COUNTRY.

93.859 - Biomedical Research and Research Training

National Institute of General Medical Sciences (NIGMS) [HHS - NIH]

Cambridge, Massachusetts 021394301 United States

Single Zip Code

Maximizing Investigators' Research Award (R35 - Clinical Trial Optional) (PAR-19-367)

Amendment Since initial award the total obligations have increased 639% from $470,880 to $3,479,127.