# Late Stage Stereochemical Editing to Transform the Synthesis of Bioactive Molecules

> **NIH NIH DP2** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $1,258,263

## Abstract

Project Summary
Chiral natural products and man-made drugs play a pivotal role in the study and treatment of a
diverse spectrum of human diseases. The presence of stereogenic centers in drug candidates
has been shown to correlate with diminished off-target toxicity, reduced CYP450 inhibition, and
an overall enhanced probability of regulatory approval as drugs. However, despite the established
importance of three-dimensionality in bioactive chemical structures, the selective synthesis of
complex organic molecules containing stereogenic centers remains a venerable challenge. The
research described in this proposal describes a conceptually new approach to the selective
formation and revision of stereogenic centers through the stereoconvergent epimerization of C–
H bonds. In contrast to the vast majority of stereoselective transformations, which establish the
absolute and relative configuration of a stereogenic center during a key bond-formation step, our
approach introduces the opportunity to enrich or invert individual stereocenters after bond
connectivity has been finalized. Our strategy thus decouples the strategies needed to establish
bond connectivity from the strategies needed to establish the three-dimensional configuration of
a complex molecule. By targeting the most ubiquitous functional group, C–H bonds, this tool has
expansive potential. If successful, the research program proposed here is anticipated to transform
chemical synthesis, dramatically reducing the time and resources necessary to synthesize
complex, bioactive molecules. Fundamental mechanistic findings revealed en route to this goal
are further anticipated to contribute significantly to our ability to understand reactivity and
selectivity patterns in the context of complex molecular environments.
.

## Key facts

- **NIH application ID:** 10245416
- **Project number:** 1DP2GM146248-01
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Alison Wendlandt
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,258,263
- **Award type:** 1
- **Project period:** 2021-09-23 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10245416

## Citation

> US National Institutes of Health, RePORTER application 10245416, Late Stage Stereochemical Editing to Transform the Synthesis of Bioactive Molecules (1DP2GM146248-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10245416. Licensed CC0.

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