Opium alkaloids. Part XVI. The biosynthesis of 1-benzylisoquinolines in Papaver somniferum. Preferred and secondary pathways; stereochemical aspects

Abstract

(–)-Tetrahydropapaverine (VI), derived from (–)-nor-reticuline (II) and (–)-nororientaline (III), is the principal immediate precursor of papaverine (VIII) in Papaver somniferum. The trimethyl ethers of papaveroline (XIa) and b) are incorporated less effectively into papaverine, the dimethyl ether (XIc) not at all. Norprotosinomenine (IV) and noriso-orientaline(V) can also be biotransformed into papaverine in the plant, but this occurs by an aberrant route which does not involve tetrahydropapaverine as an intermediate.

The stereoselectivity of various O- and N-methylations and of dehydrogenation of tetrahydropapaverine is discussed. ‘Unnatural’(–)-laudanosine was biosynthesized from ‘Unnatural’(+)-tetrahydropapaverine, but could not be obtained from ‘Unnatural’(+)-nor-reticuline. Enzymic racemization of benzyltetrahydroisoquinolines, which is a prerequisite for the biosynthesis of morphine alkaloids, appears to be limited to reticuline (Xa). N-Methylations may occur at several stages along the biosynthetic routes, and there is evidence that enzymatic N-demethylations may take place to an appreciable extent.