Nor-Laudanosoline

As part of their program of study of neuroamine metabolism in mammals, Davis and co-workers investigated the biotransformations of nor-laudanosoline (87) by rat liver and by brain preparations. They were successful in isolating a catechol O-methyltransferase enzyme system from rat liver which performed methylations of 87 to give two unidentified products (94) and later they obtained soluble enzyme preparations from rat brain and liver which, in the presence of [14C]methyl-5 -adenosylmethio-nine, gave three radioactive metabolites identified by mass spectral analysis as 90, 93, and a ring A monomethyl derivative of 93 (95, 96). 

Reticuline (67) is also a precursor for isoboldine (70) (in Papaver somniferum). Orientaline (62) has been isolated from P. somniferum for the first time, by adding inactive material as a carrier during isolation, after feeding ( + )-[3- C]nor-laudanosoline. However, it was shown not to be a precursor for isoboldine (70) in this plant, thus indicating a unique biosynthetic pathway for isoboldine from reticuline. 

Norreticuline is not a precursor for papaverine. The problem of the ease of A -demethylation in Papaver species is still not completely solved since labeled ( )-reticuline was not incorporated in papaverine while (+)-laudanosoline, which possesses the same absolute configuration as (—)-nor-laudanosoline, was incorporated. It is known that in some cases iV-demethyla-tion definitely does occur since morphine is metabolized to normorphine. ... 

Dopamine and 3,4-dihydroxyphenylpyruvic acid were added to this cell-free extract, and the formation of labelled (67), (68), and (69) was observed (carrier compounds were added at the end of the incubation). It was stated that no norlaudanosoline-1-carboxylic acid was formed under the incubation conditions when boiled enzyme was used. In none of these experiments was the chirality of the norlaudanosoline-l-carboxylic acid determined. If the reaction yielding this compound is controlled by an enz3une, one would expect this amino-acid to be optically active. The enz3une isolated by Zenk and his co-workers failed to catalyze a reaction between dopamine and 3,4-dihydroxyphenylpyruvic acid. 4-Hydroxy-phenylacetaldehyde did serve as a substrate for the enzyme. To summarize, I believe that the evidence favoring the intermediacy of norlaudanosoline-l-carboxylic acid is somewhat flimsy. It is of course possible that there are two independent routes to nor-laudanosoline, and this is the most charitable explanation of these conflicting results. 

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