1. Mammalian alkaloids: conversions of tetrahydroisoquinoline-1-carboxylic acids derived from dopamine
A Brossi Planta Med. 1991 Oct;57(7):S93-100.
Racemic and optically active mammalian 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acids derived from dopamine, and quinonemethides obtained from them by oxidative decarboxylation at physiological pH 7-9, are methylated by S-adenosyl-L-methionine in the presence of catechol-O-methyl-transferase in vitro exclusively at the OH-group at C-7. It can, therefore, be stated that these acids are unlikely intermediates in the biosynthesis of isoquinolines en route to morphine. Enantiospecific and regioselective O-methylations observed with (S)- and (R)-norcoclaurines, leading in the (S)-series predominantly to compounds methylated at the hydroxy group at C-6, and in the (R)-series to isomers methylated at the hydroxy group at C-7, respectively, are in full accord with similar reactions occurring in the plant biosynthesis of morphine. Since the same methylation pattern is ascertained in reactions catalyzed by mammalian enzymes, it is suggested that mammals might be capable of synthesizing morphine from the same isoquinoline precursors.
2. Oxidative decarboxylation of salsolinol-1-carboxylic acid to 1,2-dehydrosalsolinol: evidence for exclusive catalysis by particulate factors in rat kidney
M A Collins, B Y Cheng Arch Biochem Biophys. 1988 May 15;263(1):86-95. doi: 10.1016/0003-9861(88)90616-9.
The decarboxylation of salsolinol-1-carboxylic acid (1-methyl-6,7-dihydroxy-1,2,3,4- tetrahydroisoquinoline-1-carboxylic acid), a novel endogenous catecholic adduct of dopamine and pyruvic acid, was examined in nuclei-free homogenates of rat liver, whole brain, and kidney, as well as in buffer only. Liquid chromatographic analysis of incubations for varying times (30 min to 5 h) showed that the tetrahydroisoquinoline substrate decarboxylated oxidatively, forming one product, 1-methyl-6,7-dihydroxy-3,4-dihydroisoquinolines (1,2-dehydrosalsolinol). No salsolinol was apparent, even with added NADPH. In buffer, decarboxylation occurred by an apparent oxygen radical-mediated process: it was stimulated by cupric ion or elevated pH, and was suppressed by EDTA, superoxide dismutase, metal ion removal with Chelex-100, or low pH (less than 6). In liver or brain, the conversion was qualitatively and quantitatively similar to that in buffer; thus there was no evidence for enzyme involvement. In kidney, however, dehydrosalsolinol formation was significantly greater than that in liver, brain, or buffer, and preboiling reduced it nearly to buffer values. The heat-labile kidney activity, displaying a pH maximum ca. 9, was localized in the particulate fractions. It was blocked completely by N-ethylmaleimide. Added superoxide dismutase was only slightly inhibitory; catalase and dimethyl sulfoxide, a hydroxyl radical trap, were uneffective. Lack of inhibition by indomethacin ruled against peroxidative involvement of kidney prostaglandin synthetase. Physiological amounts of a cofactor for amino acid decarboxylases, pyridoxal-5'-phosphate, also had no effect. The oxidative decarboxylation of 1-carboxylated salsolinol by kidney fractions appears mainly due to a sulfhydryl-containing particulate factor unique to or relatively concentrated in that organ. Its identity, substrate specificity, and possible significance, particularly in alcoholism, where elevated salsolinol-1-carboxylic acid levels have been reported, remain to be ascertained.
3. Studies on the fluorophore forming reactions of various catecholamines and tetrahydroisoquinolines with glyoxylic acid
L A Svensson, A Björklund, O Lindvall Acta Chem Scand B. 1975;29(3):341-8. doi: 10.3891/acta.chem.scand.29b-0341.
Strongly fluorescent 2-carboxymethyl-3,4-dihydro-7-hydroxyisoquinolin-6-ones are formed in high yields when catecholamines are reacted with glyoxylic acid. Formation of the fluorophores has been found to take place in two steps; i. e. via virtually non-fluorescent tetrahydroisoquinoline-1-carboxylic acids, which react to give the fluorophores in a subsequent, rapid reaction with glyoxylic acid. The rates of reaction (pseudo first-order) with glyoxylic acid for 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid, and 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline-3- carboxylic acid show that introduction of a carboxyl group at either C-1 or C-3 in a tetrahydroisoquinoline highly facilitates the reaction with glyoxylic acid. This behaviour is discussed in terms of a mechanism involving both intramolecular acid catalysis by the C-1 or C-3-carboxyl groups during dehydration of the carbinolamine intermediate, and facilitation of the prototropic shifts of the resulting Schiff's base by decarboxylation.
