Norlaudanosoline-1-carboxylic acid

The terpenoid indole alkaloids are a group of plant bases derived by multiple variation on the strictosidine [(79) p. 20] skeleton. Arguably the most important work in the past five years has been done on these alkaloids with enzyme preparations from plant tissue cultures, and the research is of great potential significance for other studies in alkaloid biosynthesis. The results have allowed close definition of the early stages of biosynthesis (this Report, p. 19). Use of crude enzyme preparations in this way has been extended to the study of benzylisoquinoline biosynthesis, with enzyme-catalysed formation of norlaudanosoline-1-carboxylic acid [(57) p. 16] this compound had earlier been identified as the first of the benzylisoquinolines (this Report, p. 15). It seems that amino-acids of this general formula (6) are key intermediates in the biosynthesis of all isoquinoline alkaloids. Lophocereine (7) is exceptional in that two routes (from leucine and mevalonate) may lead to it, only one of which potentially involves an acid like (6). ... 

This scheme, first proposed several decades ago, was modified when it was postulated that DOPA was converted into the substituted pyruvic acid rather than the aldehyde, and that condensation with dopamine provided norlaudanosoline-1-carboxylic acid, which subsequently underwent decarboxylation with the eventual formation of norlaudanosoline, as is shown in route II (Fig. 2). 

Recently, Zenk et al. proved by the discovery of a novel enzyme named norlaudanosoline synthase that route I is a real pathway of benzylisoquinoline biosynthesis, and that the previously postulated intermediate norlaudanosoline-1-carboxylic acid is probably an artefact (Schumacher et al. 1983)... 

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. 

In an important series of experiments involving and doubly labeled precursors, Wilson and Coscia have shown that in Papaver orientate L., dopa may be metabolized in at least two ways to yield dopamine and 3,4-dihydroxy-phenylpyruvic acid. Decarboxylation of dopa to yield dopamine is actually favored over transamination to the substituted pyruvic acid. Norlaudanosoline carboxylic acid is the first tetrahydrobenzylisoquinoline alkaloid to be formed, and it is readily converted to norlaudanosoline through the presumed intermediacy of an imine (see Scheme 2.10). ... 

Working with Litsea glutinosa (Lauraceae), and concentrating on the biosynthesis of reticuline, Bhakuni and co-workers have shown that dopa and dopamine contribute only to the formation of the phenethylamine portion of reticuline. The benzylic portion is biosynthesized from 3,4-dihydroxyphenyl-pyruvic acid not derived from dopa. Tyrosine, 4-hydroxy-, and 3,4-dihydroxy-phenylpyruvic acid all participate in the formation of both halves of the molecule. Norlaudanosoline carboxylic acid, norlaudanosoline, and didehydronor-laudanosoline are intermediates in the biosynthetic sequence 0-methylation precedes W-methylation. ... 

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