title: Enantioselective synthesis and olfactory evaluation of bicyclic alpha- and gamma-ionone derivatives: the 3D arrangement of key molecular features relevant to the violet odor of ionones.
abstract: Violet smelling ionones 1-3, occurring in the headspace of different flowers, are well-known perfumery raw materials. With the goal to recognize the still ill-defined spatial arrangement of structural features relevant to the binding of ionones to olfactory G-protein coupled receptors, through B3LYP/6-31G(d) modeling studies we identified bicyclic compounds 7-9 as conformationally constrained 13-alkyl-substituted analogues of monocyclic alpha- and gamma-ionones. They were thus synthesized to evaluate the olfactory properties. The enantioselective syntheses of 7-9 entailed two common key steps: (i) a Diels-Alder reaction to construct the octalinic core and (ii) a Julia-Lythgoe olefination to install the alpha,beta-enone side chain. The odor thresholds of synthetic 7 and 9 were significantly lower than the corresponding parent ionones, and 9 showed the lowest threshold value among violet-smelling odorants examined so far. Modeling studies suggested a nearly identical spatial orientation of key hydrophobic and polar moieties of compounds 1, 3, and 4-9. Presumably, interaction of these moieties with ionone olfactory receptors (ORs) triggers a similar receptor code that is ultimately interpreted by the human brain as a pleasant woody-violet smell. These results open the way to studies aimed at identifying and modeling complementary binding sites on alpha-helical domains of ionone receptor proteins.
authors.affiliation: Dipartimento di Chimica Organica, Università di Pavia, Via Taramelli 10, Pavia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Luparia
authors.forename: Laura
authors.initials: L
authors.lastname: Legnani
authors.forename: Alessio
authors.initials: A
authors.lastname: Porta
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zanoni
authors.forename: Lucio
authors.initials: L
authors.lastname: Toma
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vidari