46. Mammalian Alkaloids: O-Methylation of (+/-)-Norcoclaurine-1-carboxylic Acid and Related Isoquinolines Including (S)- and (R)-Norcoclaurine with 14C-Labeled S-Adenosyl-L-Methionine in Presence of Mammalian Catechol O-Methyltransferase

Article abstract of DOI:10.1002/hlca.19900730222

(+/-)-Norcoclaurine-1-carboxylic acid (5) and the derived dihydroisoquinolinone 6 (present as quinonemethide 6a at pH 7) afforded, on methylation with 14C-labeled S-adenosyl-L-methionine in the presence of mammalian catechol O-methyltransferase, exclusively the 7-O-methylated congeners 7 and 9, respectively.High stereoselectivity of the O-methylation was observed with (-)-(S)- and (+)-(R)-norcoclaurine (2a and 2b, resp.), affording 80percent of 6-O-methylated isoquinoline 12 and 20percent of the 7-O-methylated isomer 11 from 2a, and the reversed proportion of 12 and 11 from 2b.Synthesis of the reference amino acid 8 was achieved by Pictet-Spengler condensation of O-benzyl-protected dopamine 17 with benzyl-protected keto acid 20 (-> 21) followed by methylation with diazomethane (-> 22 + 23) and removal of the protecting groups by acid hydrolysis.It is considered unlikely that amino acids such as 5 constitute important precursors in the biosynthesis of isoquinolines related to reticuline.