# New opportunities for the Cope rearrangement: methods, modular synthesis, and applications in drug discovery

> **NIH NIH R35** · UNIVERSITY OF FLORIDA · 2022 · $358,483

## Abstract

Research Summary/Abstract:
The overall goal of the Grenning research lab is to develop programable and highly diversifiable platforms for
accessing complex chemical space of interest to drug discovery. Summarized herein is an overview of work and
future directions aimed at transforming the classic Cope rearrangement into a versatile synthetic transformation
of high value for complex molecule synthesis. While variants of the Cope rearrangement (e.g. the oxy-Cope
rearrangement, aza-Cope rearrangement, and divinylcyclopropane Cope rearrangement) have found extensive
use and value in modern chemical synthesis, the classic Cope has not. This transformation is a diamond in the
rough that, post-MIRA funding, will have clear and diverse value to chemical synthesis and drug discovery. In
our published and unpublished works, we have addressed (or are addressing) fundamental challenges related
to thermodynamics and kinetics and proposed potential applications of this transformation in modular complex
molecule synthesis. Our current and future directions will involve continuing to improve our understanding of this
transformation, develop unique, complexity generating transformations and/or sequences where this
transformation plays a key role, introduce a variety of catalytic-asymmetric methods for accessing
enantioenriched building blocks, and prepare molecules of modern interest to drug discovery; a well-rounded
and diverse research program focusing both on fundamental and applied chemical discoveries. Regarding the
latter goal, we currently have on going collaborations with many medicinal chemistry and chemical biology
groups and will continue to make new connections allowing for the most impactful discoveries related to synthesis
and medicine. Funding of this proposal will result in new and general transformations of value beyond the scope
of the proposal and new leads for drug discovery. For example, we have already established a highly modular
route to Vorinostat analogs and collaboratively (with the Pflum lab at Wayne State University) will examine their
bioactivity as HDAC inhibitors. Beyond or chemistry products (methods, syntheses, and molecules), we are
requesting significant funding for the training of students and postdocs to professional synthetic chemists which
will be of critical value to a knowledgeable, scientific workforce of value to a variety of technical industries. For
example, Ph.D. graduates from my lab are currently continuing their studies as post docs (e.g. Primali Navaratne;
Stoltz Lab) or have gone directly into industry (Ehsan Fereyduni; Research Scientist at Intel).
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## Key facts

- **NIH application ID:** 10400897
- **Project number:** 5R35GM137893-03
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Alexander James Grenning
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $358,483
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10400897

## Citation

> US National Institutes of Health, RePORTER application 10400897, New opportunities for the Cope rearrangement: methods, modular synthesis, and applications in drug discovery (5R35GM137893-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10400897. Licensed CC0.

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