BIOSYNTHESIS - PART 27 - COLCHICINE - STUDIES OF THE PHENOLIC OXIDATIVE COUPLING AND RING-EXPANSION PROCESSES BASED ON INCORPORATION OF MULTIPLY LABELED 1-PHENETHYLISOQUINOLINES

Earlier research from our group had proved that the biosynthesis of co lchicine and its tropolonoid relatives involves the oxidative ring-clo sure of a 1-phenethyltetrahydroisoquinoline, autumnaline, followed by extensive modification of the cyclised product. These steps pose many mechanistic and stereochemical questions which are set out in the Intr oduction. The sequel then provides the answers based on the results fr om a series of incorporation experiments on Colchicum plants involving multiply labelled forms of autumnaline and its biological precursors. These multiply labelled samples required the synthesis of eleven diff erently labelled tetrahydroisoquinolines; the methods used to introduc e the labels are described. Autumnaline is shown to be present in Colc hicum autumnale plants and labelled forms of some precursors of it are synthesised and studied. Taken together, the findings allow further d efinition of a substantial part of the biosynthetic pathway to colchic ine and its relatives.