# Modular Synthesis of Mycotrienin I and Unnatural Ansatrienins

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $65,610

## Abstract

Project Summary/Abstract
Ansatrienins, including mycotrienin I, are natural products with high activity for the inhibition of eukaryotic protein
synthesis that act through the binding of eukaryotic elongation factors. Bacteria rely on homologous elongation
factors to synthesize proteins, yet these enzymes have not been the target of clinically useful antibiotics. Here,
I propose to develop a concise synthesis of mycotrienin I that would underpin the synthesis of unnatural
ansatrienins with novel biological activities. Elongation factors have been the targets of cytotoxic, investigational
anticancer treatments, and unnatural ansatrienins could be designed to serve the same role with a greater
therapeutic index. I will also aim to design unnatural ansatrienins that inhibit bacterial protein synthesis and do
not bind human elongation factors. Existing routes to Ansatrienins are poorly suited to the synthesis of synthetic
analogues because they are long or lack modularity, thereby hindering modification of the aromatic structure that
drives the selectivity of these natural products. The development of a modular, convergent route to this class of
natural products could form the basis of new classes of anticancer and antibiotic drugs and generate useful tool
compounds for the investigation of the elongation step in both eukaryotic and prokaryotic protein synthesis. As
existing classes of antibiotics face increasing resistance by common bacterial pathogens, the development of
new classes of antibiotics based on ansatrienins, to which resistance is unlikely to be widespread, would fill a
major unmet medical need.

## Key facts

- **NIH application ID:** 10233172
- **Project number:** 1F32GM142200-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Caleb Karmel
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $65,610
- **Award type:** 1
- **Project period:** 2021-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10233172

## Citation

> US National Institutes of Health, RePORTER application 10233172, Modular Synthesis of Mycotrienin I and Unnatural Ansatrienins (1F32GM142200-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10233172. Licensed CC0.

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