Biosynthesis. Part 25. Proof that hasubanonine and protostephanine are biosynthesised from the 1-benzylisoquinoline system

Abstract

The syntheses are described of a set of sixteen 1-benzylisoquinolines and four bisphenethylamines built from 2-(3,4-dihydroxy-5-methoxyphenyl)ethylamine (3), a known biosynthetic precursor to the alkaloids hasubanonine (1) and protostephanine (2) in Stephania japonica plants, and an acid component with a systematically varied oxygenation pattern. Administration of this set of compounds in labelled form to whole plants has resulted in incorporation of six of the 1-benzylisoquinolines into the alkaloids. The earliest of these precursors is a triphenolic tetraoxygenated isoquinoline, and subsequent oxygenation and O-methylation steps are indicated; the timing of N-methylation is not critical. These results necessitate subtle modification of earlier biogenetic speculations and rejection of some possibilities. Hasubanonine (1) and protostephanine (2) are revealed as ‘disguised’ members of the 1-benzylisoquinoline group, unique in requiring two phenolic oxygens in one of the rings undergoing oxidative coupling during their biosynthesis.