Asymmetric Synthesis of ent-Anorisol A and Its Stereoisomers and Confirmation of the Absolute Configuration of Anorisol A Isolated from Anogeissus rivularis

Abstract

AbstractAsymmetric synthesis of (2S,3S,4R,5S)-2-(2,4-dihydroxyphenyl)-5-(4-methoxyphenyl)-3,4-dimethyltetrahydrofuran, named as ent-anorisol A, was accomplished. The uncommon relative 2,3-anti-3,4-syn-4,5-syn stereochemistry across the tetrahydrofuran ring of ent-anorisol A was constructed with high yield and good stereoselectivity via an acid-catalyzed direct cyclization of unprotected chiral 1,4-diarylbutane-1,4-diol with non-symmetrical aromatic rings. Except for the sign of the specific rotation value, the spectroscopic data of the synthetic ent-anorisol A are in good agreement with those reported for natural anorisol A isolated from Anogeissus rivularis. In addition, the (2R,3S,4R,5R) and (2S,3S,4R,5R) isomers of anorisol A were also synthesized. Comparison of the specific rotation value and the experimental electronic circular dichroism data of natural anorisol A with those of the synthesized ent-anorisol A, (2R,3S,4R,5R), and (2S,3S,4R,5R) derivatives confirms the 2R,3R,4S,5R configurations assigned for natural anorisol A.