Syntheses of heterocyclic compounds. 459. Synthesis of rescinnamine-like compounds as antihypertensive agents

Abstract

Although rescinnamine (1) and reserpine (2) have essentially equal pharmacological activity the side effects of rescinnamine are weaker than those of reserpine. In hope of finding more pronounced biological activity we have synthesized some new derivatives which have a cinnamoyl sub-stituent2 at the 18 position of methyl reserpate (3).Methyl reserpate (3)3 was esterified with acid chlorides derived from 3,4-dimethoxycinnamic acid (4),4 4-ethoxy-3-methoxycinnamic acid (5),5 3,4,5-trimethoxy-2-nitrocinnamic acid (6),6 3-ethoxycarbonyl-4-methoxycinnamic acid (7),7 and 4-ethoxycarbonyl-3-methoxycinnamic acid (8)8 in pyridine-PhH to give rescinnamine-like derivatives 9,10, 11,12, and 13, respectively. Treatment of 12 and 13 with 1 equiv of NaOH in a soln of MeOH and THF at room temp gave the phenolic bases 14 and 15.