# Total Synthesis and Structural Revision of Keenamide A

## TL;DR

This paper corrects the structure of a natural peptide called keenamide A by using synthetic chemistry and NMR/X-ray analysis.

## Contribution

The paper provides a revised stereochemical configuration of the thiazoline ring in keenamide A using synthetic and analytical methods.

## Key findings

- The (R)-configuration of keenamide A's thiazoline ring was found to be incorrect and revised to (S)-configuration.
- Synthetic keenamide A stereoisomers were compared with natural samples using NMR and X-ray crystallography.
- A thiazoline-containing cyclopeptide synthesis strategy was developed and applied to this structural revision.

## Abstract

Stereochemical assignments of thiazoline-containing
cyanobactins,
a family of ribosomally synthesized and post-translationally modified
peptides, are often complicated due to the propensity of the exomethine
and C-4 chiral centers of thiazolines to epimerize under basic and
acidic conditions. In this work, we re-evaluate the proposed configuration
of the leucine-thiazoline moiety of the cyanobactin-like cyclopeptide
keenamide A. Using a fast and adaptable strategy for the synthesis
of thiazoline-containing cyclopeptides, we synthesized four possible
keenamide A stereoisomers, one of which was oxidized to mollamide
C, the thiazole analogue of keenamide A. Comparison of the NMR spectra
of synthetic keenamide A stereoisomers with that of natural keenamide
A combined with X-ray crystallographic analysis indicates that the
originally proposed (R)-configuration of the thiazoline
ring of keenamide A must be revised to (S)-configuration.
This work highlights the power of synthetic methods to inform the
structure elucidation and structural revision of natural products,
especially in cases where isolation and purification of natural material
are not readily achieved.