Studies on Cardiac Ingredients of Plants. XI. Synthesis of New Bufotoxin Homologues Utilizing Scillarenin (the Genuine Aglycone of Proscillaridin), and Their Biological Activities

Abstract

New bufotoxin homologues (3) with various lengths of alkyl chain including longer ones than a suberoyl group at C-3 of the steroid nucleus were prepared from proscillaridin (1) via its genuine aglycone, scillarenin (2), in excellent yield. In the course of preparation, we established conditions for efficient enzymatic glycolysis of 1 to give 2 quantitatively. The pharmacological activities of the resulting bufotoxin homologues (3) were evaluated by measurement of the effect on smooth muscle using the mesenteric artery from spontaneously hypertensive rats, inhibitory effect on Na⁺, K⁺-adenosine triphosphatase (ATPase) prepared from dog kidney, and positive inotropic effect (PIE) on isolated guinea-pig papillary muscle preparations. The bufotoxin homologues (3) showed only slight contraction of vascular muscle followed by a small relaxation, in addition to the high Na⁺, K⁺-ATPase inhibitory activity and PIE comparable to those of clinically used ouabain, digoxin, and digitoxin. Those bufotoxin homologues (3) may be useful as cardiac agents with a minimal vascular contractile effect.