# Metalloprotein Catalysts for Asymmetric  Synthesis

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2020 · $358,908

## Abstract

Metalloprotein catalysts for asymmetric synthesis
Project Summary
The exquisite chemo-, regio-, and stereoselectivity of enzymes make them attractive tools for organic synthesis, in
particular for the generation of chiral synthons and intermediates for the synthesis of pharmaceuticals and other
biologically active molecules. Reflecting this notion, there have been significant interest within the pharmaceutical
industry toward integrating efficient, selective, cost-effective, and sustainable enzyme-catalyzed transformations for drug
synthesis and manufacturing. Progress in this direction is critically hampered, however, by the inherently limited range of
chemical transformations catalyzed by natural enzymes as compared to those accessible through chemical methods.
Ramifications of our prior NIH-funded research have led to the discovery that myoglobin—a small, robust, and
structurally tunable heme-containing protein—, constitutes a very promising and versatile scaffold for developing
efficient and stereoselective biocatalysts for carbene transfer reactions. Building upon these exciting results, the proposed
research aims at investigating and extending the scope of these hemoprotein catalysts across a broad range of carbene-
mediated transformations useful for the construction of carbon−carbon, carbon−nitrogen, and carbon−sulfur bonds. A set
of complementary strategies will be investigated and leveraged to enhance and modulate the catalytic activity, chemo- and
stereoselectivity of these catalysts. Furthermore, valuable insights into the mechanism of these reactions and into
correlations between catalyst structure and reactivity/selectivity will be gained through a combination of experimental,
computational, and spectroscopic studies. These efforts will contribute to the definition of guiding principles and a
general, rationally driven strategy for the design and development of myoglobin-based catalysts with high activity and
fine-tuned chemo-, regio- and stereoselectivity for executing a variety of asymmetric carbene insertion reactions. These
systems will provide access to chiral building blocks of immediate value for medicinal chemistry and drug discovery
efforts. The synthetic utility of this new class of metalloprotein catalysts will be further demonstrated through their
application for the preparation of synthetically challenging drug molecules. Ultimately, this research is expected to have a
major impact toward making available new efficient, selective, and sustainable biocatalytic strategies for promoting
asymmetric carbene transfer reactions, thereby overcoming outstanding challenges in this field.

## Key facts

- **NIH application ID:** 9896830
- **Project number:** 5R01GM098628-09
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Rudi Fasan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $358,908
- **Award type:** 5
- **Project period:** 2012-06-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9896830

## Citation

> US National Institutes of Health, RePORTER application 9896830, Metalloprotein Catalysts for Asymmetric  Synthesis (5R01GM098628-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9896830. Licensed CC0.

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