Enantioselective syntheses of georgyone, arborone, and structural relatives. Relevance to the molecular-level understanding of olfaction.
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.
Hong
Sungwoo
S
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Corey
E J
EJ
D000818:Animals; D003500:Cyclization; D003510:Cyclohexanes / Q000138:chemical synthesis* / Q000378:metabolism; D007659:Ketones / Q000138:chemical synthesis* / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000378:metabolism; D009812:Odorants; D018035:Receptors, Odorant / Q000378:metabolism; D013237:Stereoisomerism
D003510:Cyclohexanes; D007659:Ketones; D009281:Naphthalenes; D018035:Receptors, Odorant; C509293:arborone; C509294:georgyone