Synthesis and Olfactory Properties of Silicon-Containing Analogs of Rosamusk, Romandolide, and Applelide: Insights into the Structural Parameters of Linear Alicyclic Musks

摘要

A series of silicon-containing derivatives of linear alicyclic musks comprising sila-Rosamusk (3b), sila-Romandolide (5b), sila-Applelide (11b), and the corresponding dehydro derivatives was synthesized from sila-analogs of Artemone and Herbac, respectively, by means of sodium borohydride reduction and subsequent esterification with the corresponding acid chlorides in the presence of triethylamine. The olfactory properties of the new sila-odorants 3b-13b are reported in comparison with their carba-analogs 3a-13a, and quantitative threshold data allowed the generation of an improved musk olfactophore model featuring a correlation of 80.5% with a null-cost distance of 244. This olfactophore model shows that it is likely that linear and macrocyclic musks address the same odorant receptors, and it should facilitate the design of new musks.