Rungrawin Chatpreecha, Chutima Kuhakarn, Pawaret Leowanawat, Vichai Reutrakul, Darunee Soorukram*

We have reported the asymmetric synthesis of three tetrahydrofuran (THF) lignans, namely (2S,3S,4R,5S)-, (2S,3S,4R,5R)-, and (2R,3S,4R,5R)-2-(2,4-dihydroxyphenyl)-5-(4-methoxyphenyl)-3,4-dimethyltetrahydrofurans, which are stereoisomers of natural anorisol A isolated from Anogeissus rivularis. The relative stereochemistry across the THF ring of each of the synthesized THF lignans was readily constructed with high yield and high stereoselectivity via an acid-catalyzed direct cyclization of the respective unprotected chiral 1,4-diarylbutane-1,4-diol bearing non-symmetrical aromatic rings. Comparison of the specific rotation values and the experimental ECD spectra of the three synthesized THF lignans with those of natural anorisol A confirms the 2R,3R,4S,5R configurations assigned for natural anorisol A. The structural and spectroscopic profiles of the synthesized stereoisomers of natural anorisol A would be of importance, especially for further development as potential chemotherapeutic agents. The developed asymmetric approach in this work highlights a practical and an atom-economic process that should also be applicable for further design of the asymmetric synthesis of other naturally occurring 2,5-diaryl-3,4-dimethyltetrahydrofurans.