THE HALOGENO-MORPHIDES AND -CODIDES, AND THE MECHANISM OF THE MORPHINE-APOMORPHINE TRANSFORMATION¹

Abstract

The halogenomorphides and halogendcodides are formed when the secondary alcoholic hydroxyl group of morphine or codeine is replaced by a halogen atom. Although the compounds occupy a position of considerable importance in the development of the morphine structural theory, and are the source of the morphine and codeine isomers, there has been no direct proof of structure offered for any single member of the series.The related pair, -chloromorphide and -chlorocodide, are the principal products obtained when morphine and codeine, respectively, are treated with thionyl chloride or phosphorus pentachloride. The halogen atom has tacitly been assumed to take the place of the hydroxyl that is known to occupy the 6-position, although it has been shown (1,2,3) in recent years that replacement of a group at this point in the nucleus often involves an a,7-shift, as a result of which the new group may appear at position 8. In carrying out numerous kilogram-scale preparations, we have observed that the a compounds are not the only products of the reaction, but are accompanied by the ß-halogeno derivatives to the extent of 10% to 15% of the total yield. In the codeine series, a-and 0-chlorocodides were obtained in part in the form of a new molecular compound of constant properties, that could not be separated into the components by fractional crystallization, although a-and ß-chlorocodides themselves differ considerably in solubility. Separation through salts, a method previously employed successfully for similar molecular compounds in the 1 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.

Microbial models of mammalian metabolism. O-Dealkylation of 10,11-dimethoxyaporphine

“…Aliquots of 5 ml were used to analyze for isoapocodeine as previously described. 26 The only metabolite detected in incubation mixtures was isoapocodeine, and the results of this experiment are shown in Figure 1. Lilly Research Centre Ltd., Erl Wood Manor, Windlesham, Surrey, England.…”

Agentes dopaminérgicos e o tratamento da disfunção erétil

“…A apomorfina (5) é um derivado sintético obtido pelo tratamento da morfina (21) com ácido clorídrico concentrado (Esquema 1) 33 . Esta apresenta similaridades estruturais com a dopamina (10), ilustradas na Figura 4.…”

Microwave‐Promoted Acid‐Catalyzed Rearrangement of Morphinans—A High‐Yield Synthesis of R(−)‐Apomorphine

“…It is well known that morphine (1) and its congeners rearrange with concentrated acids to form aporphines [1 -4] (Scheme 1). However, the yields of the conversion of morphine (1) to apomorphine (4) [1,2] and codeine (2) to apocodeine (5) [3] are low, even using a variety of acids. Granchelli et al [4] investigated the acid-catalyzed rearrangement of thebaine (3) with methanesulfonic acid, which resulted in the formation of 2,10-dimethoxy-11-hydroxyaporphine (6) in 60% yield.…”