Mycoplanecin A

Mycoplanecin A, first isolated in 1983 from the fermentation broth of Actinoplanes awajinensis subsp. mycoplanecinus. Despite its early discovery, significant renewed interest in mycoplanecin A has emerged by recent investigations. These studies confirmed its remarkable potency against Mtb with a minimum inhibitory concentration (MIC) significantly lower than that of the related griselimycins.

  • A. Torikata, R. Enokita, T. Okazaki, M. Nakajima, S. Iwado, T. Haneishi, M. Arai, J. Antibiot. 1983, 36, 957–960. 

  • M. Nakajima, A. Torikata, Y. Ichikawa, T. Katayama, A. Shiraishi, T. Haneishi, A. Mamoru, J. Antibiot. 1983, 36, 961–966.

  • C. Fu, Y. Liu, C. Walt, S. Rasheed, C. D. Bader, P. Lukat, M. Neuber, F. P. J. Haeckl, W. Blankenfeldt, O. V. Kalinina, R. Müller, Nat. Commun. 2024, 15, 791.

 

The first total synthesis of mycoplanecin A, a potent antitubercular macrocyclic depsipeptide natural product targeting the DnaN sliding clamp, is described. Interesting key steps are the synthesis of the two trans-4-alkylated-L-prolines via an iterative Matteson homologation and an O→N acyl shift observed during the fragment coupling of the building blocks. The challenging macrocyclization of the globally deprotected linear precursor was accomplished under optimized high-temperature, high-dilution conditions. This work provides chemical access to mycoplanecin A, enabling further biological investigation and analogue development against the important pathogen Mycobacterium tuberculosis.