SYNTHESIS OF N-DEMETHYL-N-SUBSTITUTED 14-BETA-HYDROXY-ISOMORPHINE ANDDIHYDROISOMORPHINE DERIVATIVES

Some new representatives (3e-3h, 5g) of a new group of structurally re lated morphine-agonist and antagonist compounds have been prepared in stereochemically homogeneous forms. Application of the Mitsunobu-react ion for suitable codeine derivatives (1a-1d) gave the benzoates (2a-2d ) of the hitherto unknown C-6 iso-compounds, which were converted into the desired isocodeines (3b-3d) by means of alkaline hydrolysis. O-De methylation of these derivatives afforded the corresponding morphine a nalogues. The preparation of 3e was also carried out from If via compo und (2e). A hitherto unknown N-demethylation also allowed the conversi on of 3a and 5a into the target compounds. With the exception of N-all yl derivatives, the dihydro analogues were obtained by the hydrogenati on of the C-7-C-8 double bond.