Morphinone-biosynthetic pathway starting from reticuline leading to thebaine and morphine

F. Morphinone 

It has been observed that the later stages of the biosynthetic pathway starting from reticuline leading to thebaine and morphine are strategically modified in some strains of opium poppy. Therefore, in such strains, thebaine is converted by way of oripavine and morphinone. In this pathway the phenolic O-methyl function is removed before that of the enol ether, i.e., accomplishing the same steps but in a different order. In other words, morphinone is obtained by the demethylation of oripavine as shown below:

Biosynthesis of Morphine, Codeine, Thebaine, Oripavine and Morphinone The various steps involved are as follows:

1. (R)-Reticuline, may be redrawn as shown in page 495 following pathway is found to be the substrate for one-electron oxidation via the phenol moiety present in each ring thereby yielding the diradical.

2. Subsequent coupling ortho to the phenol group in the tetrahydroisoquinoline nucleus, and para to the phenol in the benzyl substituent, gives rise to salutaridine—a dienone which is found as minor alkaloidal component in the opium poppy Papaver somniferum.

3. Thebaine is achieved via salutaridinol produced from salutaridine by means of the stereospecific reduction of the carbonyl group.

4. In thebaine the ring closure to form the ether linkage is caused due to the nucleophilic attack of the phenol moiety on the dienol system followed by a displacement of the hydroxyl group.

5. Future reactions essentially involve conversion of thebaine into morphine via codeine by virtue of a process that exclusively modifies the oxidation state of the diene ring, but apparently removes two O-methyl groups.

6. One is evidently present as an enol ether, removal of which yields neopinone, that subsequently gives rise to codeinone and then sodeine by the help of allylic isomerisation and reduction respectively.

7. In certain specific strains of opium poppy, thebaine is changed to oripavine and morphinone by virtue of the pathway that essentially removes the phenolic O-methyl function before that of the enol ether.

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* Kiselev and Konovalova J. Gen. Chem. USSR, 18, 142 (1948).