Constructing conformationally constrained macrobicyclic musks.

P Kraft; R Cadalbert

doi:10.1002/1521-3765(20010803)7:15<3254::aid-chem3254>3.0.co;2-#

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PubMed · 11531111

Constructing conformationally constrained macrobicyclic musks.

P Kraft·R Cadalbert

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Abstract

To investigate the structure-odor correlation of musks, (12R)-12-methyl-13-tridecanolide (1), a macrocyclic musk, and 13-tridecanolide, its non-musky 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, alpha-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.

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Bridged Bicyclo Compounds Cyclization Fatty Acids, Monounsaturated Models, Molecular Molecular Conformation Odorants Structure-Activity Relationship Journal Article Research Support, Non-U.S. Gov't

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P Kraft, R Cadalbert. 2001-08-03. Constructing conformationally constrained macrobicyclic musks.. https://doi.org/10.1002/1521-3765(20010803)7%3A15%3C3254%3A%3Aaid-chem3254%3E3.0.co%3B2-%23

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