R35GM145239

The synthesis of bioactive natural products as a driving force for discovery in organic chemistry - Project Summary/Abstract:

The objective of this research program is to discover and develop new reaction methodology en route to the synthesis of complex bioactive molecules. Our proposed studies will focus on the investigation and optimization of technologies that enable the synthesis of core structural and stereochemical subunits prevalent in many bioactive, polycyclic natural products.

The processes that we develop will find utility in the synthesis of a wide variety of structures for which there are currently no efficient synthetic roadmaps. Importantly, the methods presented in this application will be useful outside of the contexts described herein and will arm practitioners of synthetic chemistry (in academic, government, and industrial laboratories) with a new set of important tools to access enantioenriched and functionally diverse chemical building blocks for synthesis.

The research proposed in this grant application is focused on:

A) The development of new stereoselective reactions that produce densely substituted building blocks for synthesis.

B) The development of transition metal catalyzed reactions for asymmetric alkylation, acylation, and hydrogenation processes.

C) The development of these novel methods specifically for the preparation of building blocks containing all-carbon quaternary stereocenters and arrays of stereocenters.

D) The implementation of these new tactics in the syntheses of highly complex, bioactive natural products.

These molecules are not only important from a biological standpoint, they also serve as a testing ground for our new technologies. As a consequence of this approach, we will have access to:

A) Novel, medicinally relevant structures.

B) A general platform for their synthesis.

C) New synthetic methodology that will impact a host of diverse applications.

California 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 FUTURE SCIENTISTS AND DEVELOPING RESEARCH CAPACITY THROUGHOUT THE COUNTRY.

93.859 - Biomedical Research and Research Training

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

Pasadena, California 911250001 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 736% from $374,179 to $3,128,437.