Enantioselective total synthesis of colomitides and their absolute configuration determination and structural revision

Abstract

An efficient stereoselective synthetic approach to colomitides, 2,7-dioxabicyclo[3.2.1]octane-type natural products, is reported. Key steps are a stereocontrolled aldol reaction and a gold-catalyzed cycloisomerization. This synthetic strategy has been applied for the first asymmetric total synthesis of the proposed colomitides and their possible diastereomers. Comparison of their ¹H and ¹³C NMR spectra and specific rotations with those of the natural product revealed that the structure of colomitide A should be revised to 1c, and that the absolute stereochemistries of colomitides A and B are 2′R,4R,5R,8S,1R and 2′R,4S,5R,8S,1R.