Configuration‐Odor Relationships in 5β‐Ambrox

Abstract

(1 0. VIII. 90)The four possible A/B cis-fused diastereoisomers of Ambroxa have been synthesized and their configurations and conformations established by X-ray and NMR analysis. Only S,!l-ambrox ( = 1,2,3a,4,5,5a/1,6,7,8,9,9a,9ba -dodecahydro-3a~,6,6,9a~-tetramethylnaphtho[2,l-b]furan; 5 ) has an odor quality comparable to Ambrox". The 1,3-~ynperiplanar/diaxial conformation of the substituents at C(8) ( = C(3a)) and C(10) ( = C(9a)) has thus been confirmed to he a compulsory structure element for the particular odor.

Spirocyclic Ethers Related to Ambrox®: Synthesis and Structure‐Odor Relationships

“…The odor descriptions of the obtained spiro ethers 4 ± 10 ( Table 1) establish that the inactivity prediction for compound 10 is fully verified, whereas the odor of its diastereoisomer 9 is mainly woody; this result may be compared to the odor-quality alteration and odor-strength reduction observed for compound 3 relative to 1, as reported by Ohloff and co-workers [3b] [17]. In this respect, the critical arrangement of the 3a-and 9a-Me substituents in decalin-type ambergris odorants had been established [17], while the importance of the geometric position of the O-functionality relative to the axial 3a-and 9a-Me substituents in 1 was pointed out in an analysis of the superimposition of 1 with two non-decalin-type ambergris odorants [18]. Returning to Table 1, the only two compounds (i.e., 4 and 8) that evoke the ambergris descriptor, are those with the largest solvent-accessible surface area for the ether O-atom (see Fig.…”

ChemInform Abstract: Internal Nucleophilic Termination in Acid‐Mediated Polyene Cyclizations: Synthetic Access to Methyl Homologs of (.+‐.)‐Ambrox and Its Diastereoisomers.

“…MS: 296 (10, M( 79 Br 81 Br) + ), 217 (23), 215 (24), 135 (100), 121 (57), 107 (59), 93 (80). 1,2,3,4,5,6,8,. A soln.…”

“…afforded 4 (1.5 g, 73% (2 H). 13 C-NMR: 212.8 (s, C (7)); 140.1 (s, C(9a)); 132.8 (s, C(4a)); 44.0 (t, C (8)); 42.4 (t, C(6)); 39.2 (t, C (2)); 35.0 (s, C(1)); 32.5 (t, C(4)); 30.0 (t, C(5)); 27.7 (q, MeÀC (1)); 23.4 (t, C(9)); 19.6 (t, C (3) 3- (2,3,4,5,6,7,8,propan-1-ol (5; (E)/(Z) 1 : 1). At À 208 1.6M BuLi in hexane (50 ml, 0.08 mol) was added dropwise during 20 min to a stirred slurry of (3-hydroxypropyl)triphenylphosphonium bromide (18 g, 0.05 mol) in THF (130 ml) under N 2 .…”

“…(7E) 3,4,5,6,7,8, Tosylhydrazone ((E)-9). A stirred mixture of (E)-7 (200 mg, 0.55 mmol) and tosylhydrazide (= 4-methylbenzenesulfonic acid hydrazide; 120 mg, 0.65 mmol) in EtOH (2 ml (7Z) 3,4,5,6,7,8, Tosylhydrazone ((Z)-9). As described for (E)-9, with (Z)-7 (280 mg, 0.77 mmol), tosylhydrazide (170 mg, 0.91 mmol), and EtOH (3 ml) (75 min).…”

“…-The relationship between the organoleptic properties of a compound and its chemical structure has been studied extensively [2]. The ambergristype odor in particular, exemplified by the benchmark odorant Ambrox ® 2 ), has attracted special attention, and has been the subject of various theories, one of which is the empirical 'triaxial rule of odor sensation' [4]. Thus, a multi-point interaction between a dimethyl-trans-decalin skeleton and the complementary receptor site is considered to be associated with the axial orientation of the substituents R', R'', and R a , as shown in structure A.…”