Enantioselective Synthesis of the Bisabolane Sesquiterpene (+)-1-Hydroxy-1,3,5-Bisabolatrien-10-one and Revision of its Absolute Configuration

Abstract

The enantioselective synthesis of ( S)-1-hydroxy-1,3,5-bisabolatrien-10-one 1 is here described. This sesquiterpene was prepared using ( S)-3-(2-methoxy-4-methyl-phenyl)butan-1-ol as a chiral building block. Two different pathways were employed and both turned out to be high yielding, affording 1 in good chemical purity and without any racemization of the existing stereocenter. The spectroscopic data of the synthetic ( S)-1 were in very good agreement with those reported for the natural compound, which was extracted from Juniperus formosana heartwood and from the leaves of J. chinensis. The positive sign of the measured optical rotation value of synthetic ( S)-1 allows the unambiguous assignment of the absolute configuration of (+)-1 as the ( S)-enantiomer. This finding corrects the previous configuration determination which indicated the opposite result. At last, since even ( R)-3-(2-methoxy-4-methyl-phenyl)butan-1-ol is preparable in high enantiomer purity by mean of a different biocatalytic process, the formal synthesis of natural ( R)-1 was also accomplished.