# Innovation in Catalyst and Oxidative Amination Reaction Development for the Synthesis of Darobactin and Other Ribosomally Synthesized Post-translationally Modified Peptides (RiPPs)

> **NIH NIH R01** · EMORY UNIVERSITY · 2022 · $303,560

## Abstract

Project Summary
In this proposal we have outlined a plan to develop a new family of planar chiral indenyl Co, Rh,
and Ir catalysts that will be broadly applicable in the development of new oxidative amination
reactions. This represents a significant innovation in catalysis. Catalyst development is presented
in the context of allylic C-H functionalizations, which represent a contemporary frontier of group
IX metal catalysis, in which C-H functionalization relies on the innate reactivity of the C-H bond,
and does not require a Lewis basic directing group. Our preliminary results support the hypothesis
that the rhodium catalysts described in this proposal will enable a significantly expanded pool of
viable nucleophiles and alkene substrates when compared to prior state-of-the-art palladium
catalyzed allylic C-H functionalization. Mechanistic studies demonstrate that the parent RhCp*
platform provides products via a common allylic acetate intermediate, obtained via oxidatively
induced reductive elimination. These mechanistic investigations provide hypothesis driven 2nd
generation catalyst and reaction designs to control regio- and enantioselectivity. Preliminary
results demonstrate that the new catalyst platform is broadly applicable for enantioselective
catalysis beyond allylic C-H functionalization reactions. The full development of these reactions
represents a particularly significant advance in the synthesis of non-canonical amino acids,
peptides, and amide containing natural products and pharmaceuticals. The new reactions and
catalysts are developed for the synthesis of emerging ribosomally synthesized posttranslationally
modified peptide (RiPP) natural products, discovered through bioinformatic analysis, and
presenting novel structural motifs. In the long term, the realization of the chemistry described in
this proposal will provide powerful new tools for drug discovery chemists to invent new
pharmaceuticals.

## Key facts

- **NIH application ID:** 10469565
- **Project number:** 5R01GM136880-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Simon B. Blakey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $303,560
- **Award type:** 5
- **Project period:** 2020-09-20 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10469565

## Citation

> US National Institutes of Health, RePORTER application 10469565, Innovation in Catalyst and Oxidative Amination Reaction Development for the Synthesis of Darobactin and Other Ribosomally Synthesized Post-translationally Modified Peptides (RiPPs) (5R01GM136880-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10469565. Licensed CC0.

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