Enantioselective total synthesis of irniine and bgugaine, bioactive 2-alkylpyrrolidine alkaloids

An asymmetric total synthesis of the 2-(R)-alkylpyrrolidines, (-)-irniine (1a) and (-)-bgugaine (1b), toxic and antibiotic components of the tubers of Arisarum vulgare, and (+)-(S)-irniine (1c), was carried out by condensation of the corresponding 4-oxoalkanoic acid (9) with chiral phenylglycinol. Acids (9) were prepared from a hetero-organocuprate (I) complex, generated by reaction of methylcopper (I) with alkylmagnesium bromides and methyl chlorocarbonyl-propionate. Alkaloids (1a, 1b and 1c) displayed anti Gram(+) bacterial (MIC 12.5 - 50 mu g/ml) and antifungal (MIC 6.25 - 50 mu g/ml) activities.