# Stereoselective Rearrangements for the Synthesis of Bioactive Small Molecules

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $342,016

## Abstract

Project Summary/Abstract
Stereoselective chemical reactions have transformed the practice of human medicine by
providing access to chemical tools to study biological systems and pharmaceutical drugs to treat
disease. Although several methods exist for the synthesis of biologically valuable chiral
compounds, there is great potential for discovering conceptually novel strategies in catalysis for
the stereoselective synthesis of molecules not easily accessed by known methods. In particular,
there are many synthetically useful reactions that are underdeveloped in the realm of
asymmetric metal catalysis. We propose to develop the first stereoselective and regioselective
allylic oxidation of internal olefins via a hetero-ene reaction and a new approach to synthesizing
halogenated compounds via stereoselective halonium ylide rearrangements. Our long-term
goals for this research program include the discovery of general strategies for the catalytic
conversion of simple starting materials into structurally complex and biologically active small
molecules. We also anticipate that these methods will challenge established opinions of
chemical reactivity that have been held about certain classes of non-selective reactions for
years. We are taking advantage of unique opportunities for biomedical collaborations at UT
Southwestern Medical Center by utilizing our innovative chemical strategies to make new
discoveries in biology. The research strategy is divided into two project areas:
A. Selective Allylic Oxidation of Unactivated Internal Olefins: Project A is guided by the
innovative hypothesis that the ene reaction between internal olefins and chalcogen-based
oxidants is amenable to asymmetric catalysis, despite the propensity for facile thermal ene
reactions and the lack of models for stereoinduction with this class of hetero-enophiles.
Specific Aim A.1: Catalytic, Enantioselective, Regioselective, and E/Z Selective Allylic Oxidation
of Unactivated Internal Olefins
Specific Aim A.2: A.2: Therapeutic Agents for the Prevention and Treatment of Preterm
Premature Rupture of the Fetal Membranes and Preterm Labor – Collaboration with Ann Word
B. Enantioselective Synthesis of Halogenated Compounds: Project B is guided by the innovative
hypothesis that rearrangements of halonium ylides can be rendered stereoselective and
regioselective by chiral catalysts, despite the precedence for unselective reactions of these
intermediates.
Specific Aim B.1: Catalytic Enantioselective Rearrangements of Halonium Ylides

## Key facts

- **NIH application ID:** 9930082
- **Project number:** 5R01GM102604-09
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** UTTAM Krishan TAMBAR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $342,016
- **Award type:** 5
- **Project period:** 2012-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930082

## Citation

> US National Institutes of Health, RePORTER application 9930082, Stereoselective Rearrangements for the Synthesis of Bioactive Small Molecules (5R01GM102604-09). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9930082. Licensed CC0.

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