Click chemistry methodology in the synthesis of anabasine and cytisine conjugates with isoxazole derivatives

Abstract

Cytisine and anabasine derivatives containing an acetylenic fragment were used as building blocks in 1,3-dipolar cycloaddition reactions with substituted N-hydroxybenzenecarboximidoyl chlorides, catalyzed by copper(I) salt. The reactions with N-propargylcytisine were not selective, and the products were mixtures of 3,5-disubstituted isoxazoles and small amounts (5–8%) of 3,4-disubstituted isomers. 1,3-Dipolar cycloaddition with N-propargylanabasine afforded 3,5-disubstituted isoxazole derivatives with high regioselectivity.