Synthesis, antimicrobial and antiproliferative properties of epi-oligomycin A, the (33)-diastereomer of oligomycin A.

We describe the synthesis of epi-oligomycin A, a (33)-diastereomer of the antibiotic oligomycin A. The structure of (33)-oligomycin A was determined by elemental analysis, spectroscopic studies, including 1D and 2D NMR spectroscopy, and mass spectrometry. Isomerization of C33 hydroxyl group led to minor changes in the potency against , , and filamentous fungi whereas the activity against decreased by approximately 20-fold compared to oligomycin A.

Verification of oligomycin A structure: synthesis and biological evaluation of 33-dehydrooligomycin A.

Although, the structure of oligomycin A (1) was confirmed by spectroscopic and chemical evaluations, some crystallographic data cast doubt on the originally adopted structure of the side 2-hydroxypropyl moiety of this antibiotic. It was suggested that the side chain of the oligomycin is enol-related (2-hydroxy-1-propenyl). To clarify this matter we synthesized and evaluated 33-dehydrooligomycin A (2) prepared by the Kornblum oxidation of 33-O-mesyloligomycin A (3) by dimethyl sulfoxide.