SYNTHESIS AND OLFACTORIC ACTIVITY OF KETO-BETA-SANTALOL AND METHOXY-BETA-SANTALOL

In extension of structure-activity relationship investigations on beta -santalol, where the shape of the molecular surface was found to be of high importance, the influence of the electrostatic properties cf the molecules was investigated. Two derivatives of beta-santalol with sim ilar molecular shape but with an oxygen atom instead of carbon atoms w ere synthesized: keto-beta-santalol and methoxy-beta-santalol. These t wo oxygen-containing santalol analogues were synthesized by total synt heses starting from apocamphenilone. A common intermediate for both ta rget molecules, an appropriate bicyclic ketoaldehyde, proved to be ina pplicable. Therefore methoxy-beta-santalol was prepared by insertion o f an ethyldioxolane sidechain into apocamphenilone and completing the synthesis by five additional steps. Keto-beta-santalol was prepared on a convergent route by insertion of the already prefabricated sidechai n into the starting ketone, followed by one additional step. The prese nce of the second oxygen atom leads to the complete loss of the odour, which is the evidence that apart from the molecular shape, the electr ostatic potential has to be taken into account in molecular similarity studies of this class of compounds. (C) Elsevier, Paris.