# Chemical Synthesis of Chiral Bioactive Molecules

> **NIH NIH R35** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2023 · $594,571

## Abstract

Project Summary
 To enable the preparation of bioactive molecules with increased complexity, it is imperative to develop
both the synthetic logic (the design concepts) and the synthetic tools (the chemical reactions) to assemble
molecules with chiral centers and polycyclic frameworks. The proposed research program seeks to address
this need through chemical research in two general areas. The first research area will focus on the synthesis
of complex, highly oxidized, biologically active diterpenes. These total synthesis efforts inspire the
invention of new reactions and investigate the ability of existing reactions to solve strategic bond constructions
in complex settings. Synthetic access to these natural products will transform our ability to use them and their
synthetic derivatives as biological probes or as lead compounds for the development of new medicines. The
second research area will focus on the development of new Ni-catalyzed cross-electrophile coupling
reactions. These reactions have emerged as versatile methods for carbon–carbon bond formation that are
increasingly being adopted by chemists in academia and the pharmaceutical sectors. Despite recent
advances, several challenges remain, particularly with respect to the development of catalyst-controlled
stereoselective cross-electrophile coupling. To address these challenges, this research seeks to 1) identify
new modes of electrophile activation to broaden the scope of products that can be prepared by Ni-catalyzed
cross-electrophile coupling; 2) develop stereoselective cross-electrophile coupling reactions of small rings for
medicinal chemistry and natural product synthesis; and 3) develop enantioselective CEC reactions of
feedstock building blocks such as carboxylic acids and olefins. The expected outcomes of this research
program are two-fold: it will provide new reactions and strategies for preparing complex polycyclic molecules,
and it will provide access to medicinally relevant natural products and their derivatives. This research will be
carried out by a team composed of the PI, four chemistry graduate students and one postdoctoral researcher.
As part of this project, the graduate students and postdoctoral researchers will receive rigorous training in the
theory, methods, and strategies of organic chemistry. The successful execution of this research will provide
new tools to enable the synthesis of small molecules for the study and treatment of human disease.

## Key facts

- **NIH application ID:** 10645231
- **Project number:** 5R35GM118191-08
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Sarah Elizabeth Reisman
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $594,571
- **Award type:** 5
- **Project period:** 2016-05-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10645231

## Citation

> US National Institutes of Health, RePORTER application 10645231, Chemical Synthesis of Chiral Bioactive Molecules (5R35GM118191-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10645231. Licensed CC0.

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