Synthesis of Norfijimycin A with Activity against Mycobacterium tuberculosis

The total synthesis of norfijimycin A, a simplified analogue of the marine natural product fijimycin A, is described. Fijimycin A is a cyclic depsipeptide that has been shown to possess activity against methicillin-resistant Staphylococcus aureus. The natural product contains a rare N, beta-dimethyl leucine unit with unknown stereochemistry at the beta-carbon. To evaluate the importance of the beta-methyl group for antimicrobial activity, we introduced N-methyl leucine into the natural product scaffold. The resulting norfijimycin A was shown to possess significant activity against Mycobacterium tuberculosis, the etiological agent of tuberculosis.