The aspergillides A, B, and C (1, 2, and 3) comprise a novel class of 14-membered macrolides that were isolated by Kusumi and co-workers from the marine-derived fungus Aspergillus ostianus strain 01F313 that was cultured in a medium composed of bromine-modified artificial sea water Their structures were determined by extensive spectroscopic studies, and their absolute configurations were established by X-ray crystallography (for 1 and 2) and the modified Mosher method (for 3). These compounds contain tri-substituted tetrahydro and dihydropyran units and exhibit cytotoxicity against mouse lymphocytic leukemia cells (L1210) with LD_(50) values of 2.1, 71.0, and 2.0 μg mL~(-1), respectively. Because of their intriguing structural features and biological profile, these polyketides have attracted much attention in the synthetic community as targets for total synthesis. To date, four total syntheses of 1,six of 2, and two of 3 have been reported. Herein, we describe our total synthesis of the aspergillides A (1) and B (2) from a common macrolide intermediate by employing an interesting transannular oxy-Michael reaction as the key step.
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