Codeine, radioactive

The conversion of reticuline (44) into morphinan alkaloids, which occurs with loss of tritium from C-1 in P. somniferum (see above)," has been observed also for the formation of thebaine (46) in P. bracteatum, a plant which produces this alkaloid but not codeine or morphine. Radioactive 1,2-dehydroreticuline (47) labelled both reticuline (44) and thebaine (46), whilst radioactive reticuline again labelled thebaine (46). ° Codeinone (48) and codeine (50) are biosynthetic intermediates between thebaine (46) and morphine (51) in P. somniferum, and it was shown that (48) was efficiently reduced to (50) in P. bracteatumf It is apparent that alkaloid biosynthesis in the two plants is similar, with the important difference that in P. bracteatum the enzymes which effect demethylation of (46) are missing, and so biosynthesis goes no further than thebaine (46). 

The results of numerous labeling and feeding studies and other experimental results have established that the steps of the pathway are as indicated (Fig. 32.20). 2- " C-Tyrosine produces morphine labeled at C-9 and C-16. l- " C-Dopa-mine gives morphine labeled at C-16.3,4-Dihydroxyphenyl-alanine is readily incorporated into morphine (58), thebaine (59), narcotine (63), and papaverine (31) (Santavy, 1979). (/ ,5)-Norcoclaurine (23) and (/ ,S )-coclaurine (24) (both labeled at C-1) were incorporated into thebaine and morphine (labeled at position C-9) when fed to Papaver somniferum plants (Loeffler et al., 1987). Norlaudanosoline (26) (Fig. 32.5) is an efficient precursor of morphine. Studies of the rates of incorporation of radioactivity demonstrated the sequence thebaine (59) to codeine (62) to morphine (58). 

Poppies (Papaver somnifenim, Papaveraceae) have long been used as medicinal plants, food plants, and drugs of abuse. Morphine alkaloids are fotmd in many members of the genus Papaver, but codeine and morphine are only found in P. somnifemm. Another species, Papaver bracteatum contains thebaine. Morphine alkaloids are derived from ( )- or (R)-reticuline by series of reactions involving an oxidative coupling reaction. Radioactive labelling experiments have estabhshed the series of reactions from thebaine to codeine to morphine. The most important compotmd from a biosynthetic... 

Finally Fairbairn and El-Masry (1968) succeeded in proving the existence of bound alkaloids in poppy seeds. Poppy seeds normally contain only traces of alkaloids. The authors discovered alkaloidlike substances, codeine among them, after acid hydrolysis or pepsin digestion of ground seeds. These compounds were radioactive if the maturing capsule had been fed radioactive morphine. They also reported formation of these alkaloidlike compounds as a result of the action of a crude enzyme preparation from the plant upon morphine. 

Radioactive thebaine and codeine were isolated from the plants. Inactive codeine methyl ether, codeinone, or neopinone were added as carriers to detect any activity in these plausible intermediates between thebaine and morphine. Negligible (<0.02%) of the activity of the thebaine was detected in methyl ether. Significant activity was found in codeinone (5.4%) and neopinone (6.1 %)... 

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