THE ADDITION OF ORGANOMAGNESIUM HALIDES TO PSEUDOCODEINE TYPES. IV. NUCLEAR-SUBSTITUTED MORPHINE DERIVATIVES^*

Abstract

The work reported in this paper is part of a unification of effort by a number of agencies having responsibility for the solution of the problem of drug addiction.

Reactions of Alkoxides With Certain Hydrogenated Alkaloids of the Morphine Series

“…(Steric factors at C-5, C-6, and C-7 would in each case operate against the production of the maximum number of isomers). Similar reasoning would apply to a possible elucidation of the structure of isomethyldihydrocodeinone (11). Acknowledgment.…”

“…If one excludes the possibility that the hydrogen atom on C-5 participates in enolization (4,11), it may now be possible to plan additional non-degradative experiments directed toward assigning a position to the methyl group of methyl- dihydrocodeinone, the precursor of Metopon (4,11), for, if the methyl group is at C-5, alkoxide reduction should lead to no more than two isomers,3 whereas if the methyl group is at C-7, thereby introducing a new center of asymmetry at that carbon atom, as many as four isomers could be produced upon reduction.4…”

Recent Developments in the Chemistry of Thebaine and its Transformation Products as Pharmacological Targets

“…Small and his co-workers in the 30's showed that the action of Grignard reagents on any of several 6,7 derivatives of the opium alkaloids led to abnormal products in which alkylation at two different positions had taken place and the oxide bridge had been opened [110][111][112].…”

“…The isolation and structural characterization of numerous bismorphinans were done in the last few decades; however the presence of the conventional morphinandiene moiety was proven only in few cases. Two members of this family are somniferine (112) and O-methylsomniferine (113) isolated from a special variety of Papaver Somniferum grown in Tasmania. Australian researchers proved their identical structure by wide-range of spectrometric methods and the direct O-methylation of 112 yielding 113 (Scheme 45) [138].…”

“…Schwartz performed the transformation of N-protected codeinone (13, R=C(O)OCH 3 or C(O)OC 2 H 5 ) to dienol acetate (14) in the presence of anhydrous sodium acetate and acetic anhydride in very high yield (Scheme 4). This procedure is a slightly modified reproduction of Small's method [41].…”