STEREOSELECTIVE SYNTHESIS OF A DIBENZO[a,g]QUINOLIZINE ANALOG OF 18-HYDROXYEPIALLOYOHIMBANE

Publisher Website
Google Scholar
Abstract
Starting from cis-Δ4-cyclohexenedicarboxylic acid anhydride, a stereoselective synthesis of cis-Δ4-tetrahydrohomophthalic acid (IX) is described (Chart 1). The synthesis involves selective reduction to Δ4-tetrahydrophthalide (III) and reaction of the latter with cyanide to give miainly the cis-nitrile acid V in good yield. Alkaline hydrolysis leads to the cis-homodiacid IX which was characterized as its corresponding anhydride. The nitrile acid intermediate could be transformed to stereoisomeric decahydroisoquinolines (VIII). Bromolactonization of the cis-diacid IX afforded the bromo-γ-lactone XIII (R = Br; Chart 2) which underwent hydrogenolysis to the already described γ-lactone homoacid intermediate XV in good yield. Transformation of the latter to the dihydroisoquinoline XVIII was uneventful. Reduction with sodium borohydride gave XIX which on heating gave the two isomeric lactams XX and XXII. The former was identical to a lactam already obtained by a different route (ref. 1). The latter was reduced to the tetracyclic base XXIII which is believed to exist in conformation XXIVc. The corresponding trimethoxybenzoic acid ester was prepared and tested for reserpine-like activity. It was found to be inactive. The significance of this result is briefly discussed.