Synthesis of N-Demethyl-N-substituted 14b-Hydroxy-isomorphine and Dihydroisomorphine Derivatives

Abstract

Some new representatives (3e-3h, 5g) of a new group of structurally related morphine-agonist and antagonist compounds have been prepared in stereochemically homogeneous forms. Application of the Mitsunobu-reaction 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-Demethylation of these derivatives afforded the corresponding morphine analogues. The preparation of 3e was also carried out from 1f via compound (2e). A hitherto unknown N-demethylation also allowed the conversion of 3a and 5a into the target compounds. With the exception of N-allyl derivatives, the dihydro analogues were obtained by the hydrogenation of the C 7 -C 8 double bond