Biosynthesis of naphthylisoquinoline alkaloids: synthesis and incorporation of an advanced 13C2-labeled isoquinoline precursor

Biosynthetic studies on naphthylisoquinoline alkaloids involving a specifically [1,1′-13C2]-labeled dihydroisoquinoline 7 are described. The synthesized precursor 7 was fed to callus cultures of Triphyophyllum peltatum and the isolated secondary metabolites were characterized by spectroscopic methods (1H, 13C NMR, and INADEQUATE experiments). The unambiguous incorporation of the precursor into dioncophylline A and two minor naphthylisoquinolines, together with the formation of the labeled corresponding trans-configured tetrahydroisoquinoline, proves the implication of such advanced intermediates in the proposed biosynthetic pathway of naphthylisoquinoline alkaloids.