Total synthesis of (3R,16E,20E,23R)-(-)-eushearilide and structural determination of naturally occurring eushearilide

An asymmetric total synthesis of the proposed structure of (16Z,20E)-eushearilide, a novel 24-membered macrolide, was achieved via an enantioselective aldol reaction and 2-methyl-6-nitrobenzoic anhydride-mediated macrolactonization. The obtained synthetic compounds were not identical to the natural product. The newly proposed most likely structure of eushearilide, (+/-)-(16E,20E)-eushearilide, was determined on the basis of detailed NMR analysis, and (3R,16E,20E,23R)-(-)-eushearilide was successfully synthesized. A comparison of the optical rotation of (3R,16E,20E,23R)-(-)-eushearilide with that of the natural product confirmed that the true structure of naturally occurring eushearilide is the (3s,16E,20E,23s)-(+)-form. (C) 2015 Elsevier Ltd. All rights reserved.