Mammalian alkaloids: Synthesis and O-methylation of (S)- and (R)-3′-hydroxycoclaurine and their N-methylated analogues with S-adenosyl-L-[methyl-14C]methionine in presence of mammalian catechol O-methyltransferase

✍ Scribed by Xiao-Shu He; Dragana Tadić; Malgorzata Brzostowska; Arnold Brossi; Maureen Bell; Cyrus Creveling

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: German
• Weight: 805 KB
• Volume: 74
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19910740704

✦ Synopsis

Abstract

O‐Methylation of the optically active 3′‐hydroxycoclaurines 3a and 3b and of the N‐methylated analogs 5a,b with S‐adenosyl‐L‐[methyl‐^14^C]methionine in presence of mammalian COMT was investigated in vitro. The N‐unsubstituted (1__S__)‐ and (1__R__ )‐isomers 3a and 3b, respectively, afforded almost equal amounts of the corresponding N‐norreticuline 4 and N‐nororientaline 19, besides two unknown by‐products (see Fig. and Table 1). The N‐methylated (1__S__)‐isoquinoline 5a, on the other hand, afforded largely (S)‐orientaline ((S)‐19), while an almost equal mixture of (R)‐reticuline (6b) and (R)‐orientaline ((R)‐19) was obtained from the (1__R__)‐enantiomer 5b. The isoquinolines 3a,b and 5a,b were prepared by a Bischler‐Napieralski cyclization yielding O‐benzyl‐protected isoquinoline 10 (Scheme 1). The optical resolution of 10 was accomplished with 2′‐bromotartranilic acid. The N‐methylated isoquinolines were prepared by N‐formylation of 10a,b and reduction of the formamides 13a,b with diborane (→ 14a,b). Deblocking of the benzyl‐ether moieties of 10a,b and 14a,b was accomplished by catalytic hydrogenation in presence of HCl, affording directly 3a,b·HCl and 5a,b·HCl, respectively.