Search for new membrane-active substances: synthesis of tropan-3-ols with alkyl, alkenyl and alkenynyl groups at the bridgehead
Abstract
The synthesis of tropan-3-ols with alkyl, alkenyl, and alkynyl groups at the bridgehead is described. The new compounds have been considered as new membrane-active substances that would serve as model compounds for histrionicotoxin (1). Application of the Noyori route to 2-substituted pyrroles was unsuccessful. In order to avoid difficulties in obtaining individual long-chain 4-keto aldehydes for the Robinson condensation of each new model compound a key tropane intermediate (8) was prepared instead. The first attempts to extend the chains of the mesyl ester of the diol (8b) and iodomethyltropanol (9b) by Grignard type coupling failed. Therefore we embarked on a Wittig reaction of the tropane-1-carbaldehyde (11) synthesized in high yield from the diol (8). Indeed, both pent-1-enyl- and pentyltropanols, (12) and (13) were obtained. Coupling with an acetylenic phosphorane led to the pent-1-enynyltropanol (14). A further new key compound, namely 3β-acetoxytropan-1-ylacetaldehyde (15) was also synthesized as a precursor to conjugated tropanyl enynes which would more closely resemble the natural product (1).