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

Abstract An asymmetric total synthesis of the proposed structure of (16 Z ,20 E )-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, (±)-(16 E ,20 E )-eushearilide, was determined on the basis of detailed NMR analysis, and (3 R ,16 E ,20 E ,23 R )-( − )-eushearilide was successfully synthesized. A comparison of the optical rotation of (3 R ,16 E ,20 E ,23 R )-( − )-eushearilide with that of the natural product confirmed that the true structure of naturally occurring eushearilide is the (3 S ,16 E ,20 E ,23 S )-(+)-form.