Enantioselective syntheses of georgyone, arborone, and structural relatives. Relevance to the molecular-level understanding of olfaction

Abstract

Georgyone (1) and arborone (2), powerful woody odorants, have been synthesized enantioselectively along with their enantiomers. Several structural relatives of 1 and 2 have also been made enantioselectivity in order to probe the molecular details of the binding of 1 and 2 to the olfactory G-protein-coupled receptors which they activate. These studies have led to a number of conclusions regarding the structural requirements for woody odor, including absolute configuration, critical methyl substitution, and the spatial orientation of the key methyl groups. Odorants 1 and 2 bind to at least 10 mouse olfactory receptors, lending support to the combinatorial model for odor perception/differentiation. The implications of this work with regard to possible receptor binding modes are discussed.