Chemical synthesis of tetracyclic terpenes and evaluation of antagonistic activity on endothelin-A receptors and voltage-gated calcium channels.

ABSTRACT: A class of tetracyclic terpenes was synthesized and evaluated for antagonistic activity of endothelin-1 (ET-1) induced vasoconstriction and inhibitory activity of voltage-activated Ca(2+) channels. Three repeated Robinson annulation reactions were utilized to construct the tetracyclic molecules. A stereoselective reductive Robinson annulation was discovered for the formation of optically pure tricyclic terpenes. Stereoselective addition of cyanide to the hindered α-face of tetracyclic enone (-)-18 was found and subsequent transformation into the aldehyde function was affected by the formation of bicyclic hemiiminal (-)-4. Six selected synthetic tetracyclic terpenes show inhibitory activities in ET-1 induced vasoconstriction in the gerbil spiral modiolar artery with putative affinity consta

SUBMITTER: Lu J 

PROVIDER: S-EPMC4555001 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature