Mescaline biosynthesis

Morphine and codeine biosynthesis (Samuelsson, 1999 Herbert et al., 2000 Novak et al., 2000) Studies on the biosynthesis of morphine have been carried out mainly on cell cultures mainly of Coptis japonica and species of Thalictrum. Two enzymes (tyrosine decarboxylase and phenolase) catalyze the formation of dopamine from one molecule tyrosine. Dopamine is also the key intermediate in the biosynthesis of mescaline. 

Scheme 27 Biosynthesis of morphine conversion of dopamine to mescaline.

Although 3-hydroxy-4,5-dimethoxyphenethylamine is a very poor precursor of mescaline,it was found to be efficiently utilised in the biosynthesis of anhalamine (58) and anhalonidine (59) in L. williamsii. Further, the results indicated that mescaline and these isoquinoline alkaloids share a common pathway until appropriate methylation of 3,4-dihydroxy-5-methoxyphenethyl-amine brings about a divergence. 

Phenethylamines.— The biosynthesis of phenethylamines, e.g. mescaline (197), in cactus plants has been the subject of an exhaustive study. The pathways to these bases and the related isoquinolines, e.g. anhalonidine (12), is now well understood. 

The difficulties which may be encountered in establishing well-known pathways in a new plant are illustrated by feeding experiments with [2 - " C]tyrosine, [l, 2 - H2]dopamine, and 3-hydroxy-4-methoxy[ar- H]phenylethylamine in E. merkei The conversion of tyrosine into hordenine (63), established in barley could not be demonstrated. Nor were tyrosine and dopamine incorporated into salsoline (55), but all three of the labelled compounds were converted into 3,4-dimethoxyphenylethylamine. These results were rationalized as indicating a pathway that diverged after dopamine with appropriate methylation, giving either salsoline (55) or 3,4-dimethoxyphenylethylamine (a similar branch point is observed in L. williamsii for the biosynthesis of mescaline and tetrahydroiso-quinolines). Further, at the time of the experiments the required methyl-transferases for salsoline and hordenine biosynthesis were apparently blocked. In any event the pathway to 3,4-dimethoxyphenylethylamine is manifestly the dominant one, as this alkaloid and its iV-methyl derivatives are major constituent bases of this plant. 

Both the biosynthesis and chemical synthesis are based on a Mannich condensation of a -phenylethyl-amine derivative with a carbonyl component (Fig.). Depending on the latter, the substituent at Cl can be H-, CH3- or an isoprenoid residue. Several molecules of A. a. can be linked to form oligomers by phenol oxidation, as in pilocereine. As secondary alkaloids, cacti also produce derivatives of p-phenylethylamine, e. g. hordenine and mescaline. 

Barton DHR, Cohen T (1957) In Festschrift Dr A Stoll, Birkhauser, Basel, p 117 Barton DHR, Kirby GW, Taylor JB, Thomas GM (1963) Phenol oxidation and biosynthesis, part VI. The biogenesis of amaryllidaceae alkaloids. J Chem Soc 4545—4558 Barton DHR, Hesse RH, Kirby GW (1965) Phenol oxidation and biosynthesis, part VIII. Investigations on the biosynthesis of berberine and protopine. J Chem Soc 6379-6389 Barton DHR, Bracho RD, Potter CJ, Widdowson DA (1974) Phenol oxidation and biosynthesis, part XXIV. Origin of chirality in the erythrinan system and derivation of the lactone rings of a- and ]3-erythroidine. J Chem Soc Perkin Trans 1 2278-2283 Basmadjian GP, Paul AG (1971) The isolation of an O-methyltransferase from peyote and its role in the biosynthesis of mescaline. Uoydia 34 91-93 Basmadjian GP, Hussain SF, Paul AG (1978) Biosynthetic relationships between phenethylamine and tetrahydroisoquinoline alkaloids in peyote. Lloydia 41 375-380 Battersby AR, Binks R, Francis RJ, McCaldin DJ, Ramuz H (1964) Alkaloid biosynthesis, part IV. 1-Benzylisoquinolines as precursors of thebaine, codeine and morphine. J Chem Soc 3600-3610... 

Tyrosine serves as substrate for the biosynthesis of important natural products. Historically, morphine and mescaline have attracted considerable attention from ancient cultures. 

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