To investigate the structure ยฑ odor correlation of musks, (12R)-12methyl-13-tridecanolide (1), a macrocyclic musk, and 13-tridecanolide, its nonmusky demethyl analogue, were conformationally constrained by introduction of methylene bridges between C-3 and C-8 or C-9. These [7.5.1]-and [8.4.1]macrobicycles were synthesized starting from bicyclo[5.3.1]undec-8-en-9-one (3) and bicyclo[4.3.1]dec-7-en-8-one (8), respectively, by a sequence consisting of catalytic hydrogenation, a-alkylation with a TBS-protected (tert-butyldimethylsilyl) hydroxy halide, acid-catalyzed cyclization, oxidative cleavage of the formed enol ether double bond, and subsequent reduction of the carbonyl group via its tosylhydrazone. The compound (1R,6R,9R)-()-6-methyl-4-oxa-bicyclo[7.5.1]pentadecan-3-one ( 22) was found to possess the most pronounced musk odor, and this was rationalized by a superposition analysis with the polycyclic aromatic musk odorant (4S,7R)-Galaxolide (2). In its (1S,6R,9S)-()stereoisomer 23 as well as in (1S,6R, 10R)-()-6-methyl-4-oxabicyclo[8.4.1]pentadecan-3-one ( 18) the (6R)-methyl group seems to hinder the interaction with the musk receptor, while the demethyl compounds 7 and 12 showed only very faint odors.