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Constructing Conformationally Constrained Macrobicyclic Musks
Author(s) -
Kraft Philip,
Cadalbert Riccardo
Publication year - 2001
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20010803)7:15<3254::aid-chem3254>3.0.co;2-#
Subject(s) - chemistry , polymer science
To investigate the structure–odor correlation of musks, (12 R )‐12‐methyl‐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, α ‐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 (1 R ,6 R ,9 R )‐(+)‐6‐methyl‐4‐oxabicyclo[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 (4 S ,7 R )‐Galaxolide ( 2 ). In its (1 S ,6 R ,9 S )‐(+)‐stereoisomer 23 as well as in (1 S ,6 R ,10 R )‐(+)‐6‐methyl‐4‐oxabicyclo[8.4.1]pentadecan‐3‐one ( 18 ) the (6 R )‐methyl group seems to hinder the interaction with the musk receptor, while the demethyl compounds 7 and 12 showed only very faint odors.