Enantioselective Synthesis of Strobamine and its Analogues

(2S,5S,8R)-Strobamine (+)-1a was synthesized by adding cinnamoyl cyanide 6a to tropinone 3 lithium enolate generated by treatment of (S,S')-alpha, alpha-dimethyldibenzylamide with butyl lithium in the presence of lithium chloride to give (-)-chalcostrobamine (-)-7a, which yielded a one-to-one mixture of (+)-1a and its C-2 epimer (-)-2a on treatment with 2N sulfuric acid. Compounds (+)-1a and (-)-2a could be separated by column chromatography. (-)-Strobamine (-)-1a and (+)-2a were synthesized by a similar set of reactions using the tropinone 3 lithium enolate generated with butyl lithium in the presence of (R,R')-alpha, alpha'-dimethyldibenzylamide and lithium chloride. (+)- and (-)-p-Methylstrobamine (+)- and (-)-1b and (+)- and (-)-epi-p-methylstrobamine (+)- and (-)-2b were synthesized by a similar procedure. The absolute configuration of (+)-epi-p-methylstrobamine (+)-2b was determined by X-ray analysis to have the (2S,5R,8S) configuration.
Pub. in Arkat USA Inc,, p96-103. ISSN 1551-7012.