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 car ried 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 o f this type. This analysis showed that the presence of both a carbonyl group and a quaternary carbon atom connected to a methyl group is suf ficient for compounds to have the androstenone odor if a topological d istance between the carbonyl oxygen and the quaternary carbon is equal to eight C-C and/or C - 0 bonds, the geometrical distance between the m is 8.5 angstrom, and the maximum distance between the carbonyl oxyge n 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 t ests of the synthetic compounds. The androstenone odor threshold of ke tones having this odor was decreased by alpha-methylation and it was s hown that this effect depends on the stereochemistry of the methyl gro up.