Synthesis and Cytotoxicity of 4-Hydroxy-15-Triazolyl-Substituted Isoalantolactone Derivatives

Abstract

A method for modifying ring A of isoalantolactone to produce 4(R)-hydroxy-15-triazolyl derivatives was developed. The key steps in the transformation included sequential azidolysis of 13-methoxy-4,15-epoxy- 11,13-dihydroisoalantolactones and Cu-catalyzed azide-alkyne cycloaddition with various alkynes. A retro-Michael reaction of (11R)- and (11S)-stereoisomeric (4R)-hydroxy-13-methoxy-15-triazolyl-11,13- dihydroisoalantolactones using cesium carbonate in DMF formed isoalantolactone derivatives. The structures of three compounds were established by X-ray crystal structure analyses.