Aberrant Biosynthesis of Unnatural Alkaloids

Since other methyl ethers, e.g. reticuline and its structural isomers, are not demethylated in P. somniferum, - it is concluded that only one enzyme is responsible for the O-demethylation of codeine and its derivatives. 

Biotransfonnations of Alkaloids.—For a long time it was considered that alkaloids were end-products of metabolism. However, it is now being realized that many of them are rapidly metabolized, either to other alkaloids, or to non-alkaloidal compounds. Waller and co-workers have carried out extensive work in the past few years on ricinine metabolism. In senescent leaves of Ricinus communis, ricinine (18) is demethylated to N-demethylricinine (19). In 

Another reversible reaction is the interconversion of (-i-)-coniine (20) and y-coniceine (21) which occurs in hemlock (Conium maculatum). The reaction is stereospecific, only the natural (-t-)-coniine being dehydrogenated to y-coniceine. y-Coniceine is formed in hemlock from 5-oxo5ctanal by a transamination involving L-alanine. By administering [l - C, N]coniine and [r- C, N]-y-coniceine to hemlock, and then re-isolating the alkaloids 

1 and 9 days later, it was established that there was little, if any, loss of the relative to the C. It is thus apparent that the nitrogen of these hemlock alkaloids is not removed by a reversal of their biosynthesis, or by other metabolic reactions. 

Very little is known about the non-alkaloidal metabolites of alkaloids in the species where they are formed. Fairbairn has shown that morphine is rapidly metabolized in the latex of the opium poppy to polar non-alkaloidal compounds of unknown structure. Iljin found that the administration of [ C]nicotine to tobacco led the production of many radioactive amino-acids. 

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Aberrant Biosynthesis of Unnatural Alkaloids.—Kirby S has demonstrated that the opium poppy Papaver somniferum) is capable of carrying out transformations of unnatural precursors to unnatural alkaloids. The 0natural conversion of codeine into morphine by feeding to the plant a mixture of a [2- H]codeine derivative and [N-methyl- C]codeine. One unnatural transformation which was more efficient than the natural one was the conversion of dihydrodeoxycoddne (10) into di-hydrodeoxymorphine (11) (Scheme 4). Kirby concluded that neither the 6-hydroxy-group nor the 7,8-double bond in codeine is important for binding to the enzyme responsible for demethylation of the 3-methoxy-group of codeine. 

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