Synthesis of (±)-likonide B (smenochromene D) using a regioselective Claisen rearrangement, separation of the enantiomers and stereochemical assignment

Abstract

A synthesis of the unusual ansa-bridged farnesyl hydroquinone derivative likonide B in racemic form is described. The natural product, also known as smenochromene D, was obtained from geranylacetone by a route in which the key steps are a regioselective microwave-mediated Claisen rearrangement of an aryl propargyl ether to deliver the chromene ring, and macrocyclization via an intramolecular Mitsunobu reaction. Subsequent HPLC on a chiral stationary phase gave the pure (+)- and (−)-enantiomers, that were studied by CD spectroscopy, thereby shedding some light on the true stereochemical nature of the two natural products (−)-smenochromene D and (+)-likonide B.