Mammalian alkaloids

Brossi, A. 1991. Mammalian alkaloids Conversion of tetrahydroisoquinoline-1-carboxylic acids derived from Dopamine. Planta Medica, 57 S93-S100 and, Xe, X. S., Tadic, D Brzostowska, M Brossi, A., Bell, M. and Creveling, C. 1991. Mammalian alkaloids - Synthesis and O-methylation of (S)-3 -hydroxycoclaurine and R-3 -hydroxycoclaurine and their N-methylated analogs with S-adenosyl-L-[methyl-C-14]methionine in presence of mammalian catechol O-methyltransferase. Helvetica Chimica Acta, 74 1399-1411. 

Alkaloids formed endogenously in mammals and in man are named mammalian alkaloids. These substances are closely related to, and sometimes identical with, alkaloids found in plants. The alkaloid harman, which occurs in rat brain (7), also is present in the bark of tropical trees... 

Mammalian alkaloids were reviewed in Vol. 21 of this treatise (5a) they have been referred to in connection with reviews on indole and... 

The mammalian alkaloids are formed from aromatic amino acids and their metabolically derived amines by reaction with carbonyl substrates at physiological pH. The reaction is catalyzed by acid and is commonly referred to as the Pictet-Spengler cyclization (I0a,b,II). Winterstein and Trier in 1910 proposed that the Pictet-Spengler reaction might be of significance in the biosynthesis of benzylisoquinoline alkaloids in plants (5a). The carbonyl compounds participating in the Pictet-Spengler synthesis of mammalian alkaloids are aldehydes and a-keto acids, which are produced... 

DBC 34 (harmalan) is a rare mammalian alkaloid present in goat urine (67). The fully aromatic BC 35 (norharman), on the other hand, is an endogenous metabolite in man (44), and BC 36 (harman) was found to be present in tissues of rat and man (1,46,54,68,69). Carboxylic acid 37 was detected in cerebral fluids of monkeys (70), and analog 38 was detected in bovine milk and urine (71). 

Rommelsbacher, in following the concept of Holtz that mammalian alkaloids are formed from chemically reactive biogenic amines and amino acids by reaction with endogenously formed ketonic substrates under physiological conditions, has extended this idea to include indole-3-acetaldehyde. It was found that tryptamine, on incubation with pig brain and bovine brain, but not with liver tissue, formed the thiazolidine carboxylic acid 60 shown in Fig. 20 Ml). 

Several syntheses of racemic salsolinol (64) by Pictet-Spenglercycliza-tion of dopamine with acetaldehyde have been reported 10a,150). The synthesis of the optically active (5) enantiomer TIQ 64a from the methyl ether analogs TIQs 62a and 68a by acid hydrolysis correlates the chemistry of mammalian alkaloids with that of plant isoquinolines (146-148). 

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