Total Synthesis of (+)-Machaeriol D with a Key Regio- and Stereoselective SN2 Reaction

摘要

Since its discovery in 1964, tetrahydrocannabinol (THC) and related derivatives (cannabidiol (CBD), non-natural hexahydrocannabinol (HHC)) have captured the imagination of research groups all over the world.[1] The structurally related 5,6-secohexahydrodibenzopyrans (5,6-seco-HHDBPs) machaeridiol A-C and trans-HHDBPs machaeriol A-D were recently isolated from the stem bark of Machaerium multiflorum spruce (Fabaceae) (Scheme 1).[2] Although much effort has been devoted to the synthesis of this class of natural products,[3] the stereocontrolled construction of the three or four stereocenters located on the cyclohexane ring still represents a significant synthetic challenge. Herein, a general strategy is described for the first enantioselective total synthesis of (+)-machaeriol D (1), one of the most complex HHDBPs, via a 5,6-seco-HHDBP and with an SN2 reaction[4] as a key step.