Total Synthesis of the Antibiotic Branimycin

摘要

The nargenicin antibiotics have repeatedly been the target of synthetic efforts over the past 20 years although only one synthesis has been completed so far.Branimycin (1), which was isolated from the actinomycetes strain GW 60/1571 by the Laatsch research group, is the most complex known member of this family. Biological tests have shown that branimycin is active against Escherichia coli, Bacillus subtilis, Staphylococus aureus, and in particular against Streptomyces viridochromogenes. The structure of 1, which was elucidated by multidimensional NMR experiments only, is unusually complex, as 24 out of the 25 carbon atoms are either functionalized and/or stereogenic. In total, there are 12 stereocenters, 2 double bonds, 3 secondary OH groups, and 3 CH2OMe functions. Additionally, the cis-fused dehydrode-calin core, the 7,12-ether bridge, and the nine-membered macrolide ring make 1 an attractive target for total synthesis. Herein we report the first total synthesis of 1, which also confirms the relative stereochemistry assigned by the Laatsch research group. Additionally, the absolute configuration of 1 has been established (Figure 1).