Quinuclidine chemistry. 2. Synthesis and antiinflammatory properties of 2 substituted benzhydryl 3 quinuclidinols

Article abstract of DOI:10.1021/jm00251a005

A number of 2 benzhydryl 3 quinuclidinols were tested for their anti inflammatory activity. The cis isomers were prepared selectively by aluminum isopropoxide reduction of the ketones which were made by the addition of aromatic Grignard reagents to 2 benzylidene 3 quinuclidinones. The most active compound was cis 2 (4,4' difluorobenzhydryl) 3 quinuclidinol. The trans alcohol was less active than the cis isomer. It was made by selectively oxidizing the cis alcohol in a mixture of cis and trans alcohols (formed by NaBH₄ reduction of the ketone) followed by chromatography. The two diastereoisomers of the monofluorinated alcohol, 2 (4 fluorobenzhydryl) 3 quinuclidinol, showed activity but were markedly less active than the difluorinated alcohol. The quinuclidine nitrogen was vital for activity for cis 3 (4,4 difluorobenzhydryl) bicyclo [2.2.2] octan 2 one showed only marginal activity.