Mammalian Alkaloids: Conversions of Tetrahydroisoquinoline-1-carboxylic Acids Derived from Dopamine*

Abstract

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.

Key words

Mammalian alkaloids - tetrahydroisoquinolines - O-methylation - morphine biosynthesis - dopamine - Pictet-Spengler cyclization - quinonemethides