Morphine homologues

Molecular modifications of the morphine skeleton have produced numerous derivatives with antitussive properties, some of which have become commercially significant. Ethyknorphine [76-58-4] (29), a simple homologue of codeine, is prepared by ethylating morphine. It is pharmacologically similar to codeine but is seldom used clinically. Pholcodine [509-67-1] (30), the morpholinoethyl derivative of morphine, is used as an antitussive in a number of European countries. It is about one and a half times as potent as codeine, has Htde or no analgesic activity, and produces minimal physical dependence. The compound is prepared by the amino alkylation of morphine (48). 

A number of homologues of codeine have been prepared by the alkylation of morphine for example, ethylmorphine, which is used in medicine... 

Narcotic analgesics Morphine and many of its homologues, when administered in medicinal doses, relieve pain and produce sleep. In poisonous doses, these produce stupor, coma, convulsions and ultimately death. Morphine narcotics are sometimes referred to as opiates, since they are obtained from the opium poppy. 

Morphine has a strong analgesic effect and has been used for the alleviation of postoperative and cancer pain since antiquity, but its use is now restricted because of its drug dependency. Morphine and its homologues were called opiates after opium, which was extracted from poppy seeds. This class of drugs are now termed opioids. 

The acetal for the second building block is obtained in two stages from iso-vanUlin in 96 % yield. After the introduction of iodine, the hydroxy-group is reprotected and the aldehyde converted into its homologue by reaction with a sulfur ylide, and then by Lewis acid-catalysed opening of the epoxide. In this way, there results an appropriate building block for ring A of the morphine skeleton. 

A number of homologues of codeine have been prepared by the alkylation of morphine for example, ethylmorphine, which is used in medicine in the form of the hydrochloride, CjgHasOgN. HCl. 2H2O (colourless, bitter, microcrystalline powder, m.p. 122-5°), and benzylmorphine, Ci-Hi502N(0. CHg. CjHj), also used as the hydrochloride, B. HCl. H,0, a colourless, crystalline powder. 

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