MOLECULAR DESIGN OF SUBSTANCES WITH THE ANDROSTENONE ODOR - 2,4'-SUBSTITUTED 4-CYCLOHEXYLCYCLOHEXANONES - A NEW CLASS OF ANDROSTENONE-LIKE ODORANTS

A comparative analysis of molecular topology and geometry has been carried out for known compounds with the odor of 5alpha-androst- 16-en-3-one in order to find criteria for a molecular design of new odorants of this type. This analysis showed that the presence of both a carbonyl group and a quaternary carbon atom connected to a methyl group is sufficient for compounds to have the androstenone odor if a topological distance between the carbonyl oxygen and the quaternary carbon is equal to eight C-C and/or C - 0 bonds, the geometrical distance between them is 8.5 angstrom, and the maximum distance between the carbonyl oxygen and any other atom in the molecule does not exceed 10.3 angstrom. On the basis of this analysis a new class of androstenone-like odorants, 2,4'-substituted 4-cyclohexyl-cyclohexanones and their ci-methylated derivatives, was predicted and confirmed experimentally by olfactory tests of the synthetic compounds. The androstenone odor threshold of ketones having this odor was decreased by alpha-methylation and it was shown that this effect depends on the stereochemistry of the methyl group.