Total synthesis of diastereomeric marine butenolides possessing a syn-aldol subunit at C10 and C11 and the related C11-ketone

Abstract

Two diastereomeric marine butenolides, (4 S,10 R,11 R)- and (4 S,10 S,11 S)-4,11-dihydroxy-10-methyldodec-2-en-1,4-olide, possessing a syn-aldol subunit at C10 and C11 have been efficiently synthesized by using a three-module coupling strategy. The enantiomeric syn-aldol modules prepared by the syn-selective aldol reaction of the norephedrine-derived chiral propionates were coupled with the chiral C3–C7 module via 1,3-dithiane bisalkylation. The butenolide ring was then installed via a high-yielding ring-closing metathesis (RCM) reaction. Oxidation of the diastereomeric C11-alcohols furnished the corresponding C11-ketones, which are produced by the same marine microorganism.