# Innovative Tools for Chemical Synthesis: Cyclase-inspired Catalysis, Shuttle Catalysis , and Tandem Catalysis

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA-IRVINE · 2022 · $69,757

## Abstract

Principle Investigator/Program Director (Last, first, middle): Dong, Vy, M
Project Summary/Abstract
The construction of amide bonds is a widely used chemical transformation across many disparate disciplines of
chemistry and is one of the most frequently employed disconnections in the pharmaceutical industry. As such,
efforts to improve and expand the synthetic utility of amide bond formation remain integral for multidisciplinary
reaction development and drug discovery campaigns within academic and industrial sectors. The coupling of
sterically hindered amino acids, such as therapeutically valuable α,α-disubstituted α-amino acids and derivatives
thereof, represents an underdeveloped yet promising area for amide bond formation that can be improved.
Although methods to construct difficult amide bonds are available, waste generated from either stoichiometric or
super-stoichiometric reagent use as well as possible deleterious reaction byproducts produced using
conventional approaches imposes the need to develop more sustainable protocols. Previous work from Xie and
coworkers have shown that acyl radical peptide precursors can be generated under photoredox conditions via a
P(V)/P(III) cycle, however is limited to nitroarene and nitroalkane coupling partners. Therefore, our goal is to
broaden the scope of accessing sterically hindered amide bonds catalytically by employing an umpolung
approach using a phosphorus catalyst to generate nucleophilic acyl radical amino acid partners to form hindered
secondary and tertiary amide bonds with readily accessible, electrophilic hydroxylamine esters. If successful,
this methodology could enable a more facile approach towards sterically hindered peptides that may be extended
towards additional challenging amide structural motifs.

## Key facts

- **NIH application ID:** 10649303
- **Project number:** 3R35GM127071-05S2
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Vy M Dong
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $69,757
- **Award type:** 3
- **Project period:** 2018-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10649303

## Citation

> US National Institutes of Health, RePORTER application 10649303, Innovative Tools for Chemical Synthesis: Cyclase-inspired Catalysis, Shuttle Catalysis , and Tandem Catalysis (3R35GM127071-05S2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10649303. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*