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Synthesis shows reduced antituberculosis activity of a new bicyclomarin derivative compared to cyclomarin, indicating limitations in effectiveness.
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.
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Greve et al. (2025) studied this question.
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