Codeine 14-hydroxy

Considerable progress has also been made with the alternative line of work, the search for a synthetic analgesic as effective as morphine and without its disadvantages. The work of the American Committee has shown that it is possible to produce analgesics with a dibenzofuran or carbazole nucleus in place of the phenanthrene or phcnanthrylene oxide nucleus of morphine and it is stated that synthetic products with analgesic potency equal to that of codeine have been prepared. In the 1938 report moderate analgesic potency was recorded for preparation No. 421, 9-methyl-2-(l-hydroxy-3-diethylamino)-propylcarbazole at 10 mgm. by injection. 

Lediglich in der Codein-Reihe wird in einigen Fallen die 14-Brom-Funktion durch eine Hydroxy-Gruppe ersetzt (s.S. 763) bzw. es wird Dehydrohalogenierungbeobachtet (s. S. 738). 

The inifial sfeps in fhe mefabolism of morphine and codeine by Pseudomonas putida MIO involve oxidafion of fhe C-6 hydroxy group and subsequenf reducfion of fhe 7,8-olefinic bond, forming hydromorphone (dihydromorphinone) and hydrocodone (dihydrocodeinone), respectively (Scheme 4) [52], These products have important industrial appUcations hydromorphone is an analgesic some seven times more potent than morphine [53],... 

Oxycodone The synthesis of oxycodone, 4,5-epoxy-3-methoxy-14-hydroxy-iV-methyl-6-oxomorphinane (3.1.25), from 14-hydroxycodeinone (3.1.24) was described above. It can also be synthesized in other ways for example, by the oxidation of codeine using sodium dichromate in acetic acid [17], and is also a stractural analog of morphine and codeine. 

Cortisol into 7- 3-hydroxycortisol. Epoxidation Benzene into benzene 1,2-epoxide. N-oxidation Drug containing amino groups can undergo N-oxidation i.e. imipramine into imipramine N-oxide. 0-dealkylation This reaction probably Involves formation of an unstable hydroxy methyl Intermediate I.e. codeine Into morphine. 

The diethyl compound without the iodine is 2,5-dimethoxy-N,N-diethylamphetamine, which was prepared by the reductive alkylation of DMA with acetaldehyde and sodium cyanoborohydride. This product, DEDMA, was a clear white oil, bp 82-92 °C at 0.15 mm/Hg which did not form a crystalline hydrochloride. An interesting measure of just how different these N,N-dialkylated homologues can be from the psychedelic primary amines, pharmacologically, can be seen in the published report that the beta-hydroxy derivative of DEDMA is an antitussive, with a potency the same as codeine. 

Derivatives of 14-hydroxydihydrocodeinone have been converted into 6a- and 6/ff-amino-compounds by condensation with benzylamine and then reduction and hydrogenolysis of the resulting Schiff-bases,195 and also into their hydrazones.196 Codeine and ethylmorphine have been nitrated and sulphonated at position 1197 and fluoro-compounds of structures (103 R = H), (103 R = OH), (104 R = H), and (104 R = OH) have been prepared from dihydrocodeinone and 14-hydroxy-dihydrocodeinone by treatment with diethylaminosulphur trifluoride.198... 

C19 2D6 Mephenytoin (4-hydroxy metabolite), Omeprazole Bufuralol, Dextromethorphan Metoprolol, Debrisquine, Codeine Tranylcypromine Quinidine Ticlopidine (but also inhibits 2D6), Nootkatone (but also inhibits 2A6)... 

Synonym. -Codeine. It has been incorrectly called hydroxy-codeine. 

HYDROXY CODEIN ONE, 14-B ROMO CODE IN ONE, AND THEIR DERIVATIVES... 

Treatment of 14-hydroxydihydrocodeine-B with thionyl chloride results only in chlorination of the aromatic nucleus (cf. the corresponding reaction with the four dihydrocodeine isomers, Chap. IV), but treatment with phosphorus pentachloride affords 14-hydroxy-6-chlorodihydrocodide [xrx], That the hydroxyl group at C-6 is the one that is replaced by chlorine is revealed by the fact that reduction of [xrx] by sodium amalgam and alcohol is attended by rupture of the cyclic ether link, giving 14-hydroxydihydrodesoxycodeine-C [xx], which is readily reduced catalytically to 14-hydroxytetrahydrodesoxy-codeine [xm]. All attempts to reduce [xrx] to a non-phenolic base, or to secure elimination of hydrogen chloride with production of a substance of the desoxycodeine-C type failed [6]. 

In an analogous manner 3-hydroxy-N-methylmorphinane [nxxm] was prepared from [lxxii], and when [lxxiv] was heated with hydrochloric acid at 120° C. cyclization and partial demethylation occurred, the product being dl-tetrahydrodesoxycodeine [lxxv], identical with the racemate prepared from the separate d and l isomers obtained from sinomenine and codeine respectively. The racemate was resolved by d-tartaric acid [24], Complete demethylation occurred when the cyclization was effected with hydrobromic acid, the product being dZ-tetrahydrodesoxymorphine [24],... 

Codeine dihydromethine [xn] has now been prepared by the sodium-ammonia reduction of codeine methiodide, together with dihydrodesoxy-codeine-C dihydromethine [xiii]. Both [xii] and [xni] result from the sodium and liquid ammonia reduction of a-codeimethine [xiv] [2] (cf. p. 106). The sodium and liquid ammonia reduction of dihydrocodeine methiodide affords a-tetrahydrocodeimethine, and the reduction of /3-codeimethine [xv] yields neopine dihydromethine [xvi]. When the methiodide of the latter is heated with sodium cyciohexyloxide in cyciohexanol a mixture of methyl-morphenol [xvn] and (-f-)-6-hydroxy-3-methoxy-5 6 7 8 9 10-hexahydro-phenanthrylene-4 5-oxide [xviii] is obtained. The latter structure is assigned to the product on account of the close resemblance of its ultra-violet absorption spectrum to that of a-codeimethine. This represents a new type of degradation with hydrolytic scission of the side-chain [2]. Metathebainone methine has also been degraded in this way [2]. 

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