Stereochemistry‐Odor Relationships in Enantiomeric Ambergris Fragrances

Abstract Twelve tricyclic ethers of the labdane and ent ‐labdane series, 5–16 , have been synthesized; compounds 6–15 are new. The intramolecular C 18 ‐acetals 1–4 and the tricyclic ethers 5–16 were submitted to an olfactory test which was characterized by an exceptionally high percentage of ‘wrong’ answers ( cf. Table 1 , footnote b). For most compounds specific anosmia, rapidly ensuing fatigue and a high percentage of odor deviation were the most salient features. Pronounced ambergris‐like odors were only noted in compounds of the labdane series, and were strongest in ethers 1, 5 and 15 , followed by the ethers 9 and 11 . In contrast, both labdane derivatives 3 and 7 were practically odorless. Their enantiomers 4 and 8 , on the other hand, have relatively strong odors which can only to a limited extent be associated with ambergris‐type odors. The pairs of ethers 3/4 and 7/8 are the first recorded examples of optical antipodes in which only one isomer possesses olfactory properties.