# Synthesis of a Conformationally Fixed Bicyclomarin Derivative

## TL;DR

Scientists synthesized a new bicyclic version of cyclomarin to improve its antituberculosis activity, but the new compound was less effective than the original.

## Contribution

A conformationally fixed bicyclic derivative of cyclomarin was synthesized and evaluated for antituberculosis activity.

## Key findings

- The linear heptapeptide and macrolactamizations were successfully synthesized.
- The final benzyl ether cleavage step had low yield.
- The bicyclic compound showed reduced antituberculosis activity compared to cyclomarin.

## Abstract

Based on an X‐ray structure of cyclomarin bound to ClpC1, a new conformationally fixed, bicyclic cyclomarin derivative is synthesized in an effort to enhance antituberculosis activity. The synthesis of the linear heptapeptide and the two macrolactamizations proceed smoothly. Only the very last synthetic step, the cleavage of a benzyl ether, provides a low yield. Despite the successful synthesis, the resulting bicyclic compound shows reduced activity compared to cyclomarin.

The synthesis of a new bicyclic derivative of cyclomarin is described. Cyclomarin is a marine cyclopeptide with excellent antituberculosis activity. The synthesis of the linear heptapeptide and the two macrolactamizations proceed smoothly.© 2025 WILEY‐VCH GmbH