5′-O-Methyldioncophylline D, a 7,8′-coupled naphthylisoquinoline alkaloid from callus cultures of Triphyophyllum peltatum, and its biosynthesis from a late-stage tetrahydroisoquinoline precursor

Abstract

The natural tetrahydroisoquinoline phylline (4) was synthesized in a specifically [1,1'-C-13(2)]-labeled form, and fed to callus cultures of Triphyophyllum peltatum. Its incorporation into naphthylisoquinoline alkaloids, among them habropetaline A (8) (as evidenced by H-1, C-13 NMR, and 2D INADEQUATE experiments), proved 4 to be the authentic coupling substrate for the enzyme-mediated phenol-oxidative coupling with a naphthalene portion. During the feeding experiments, a new alkaloid was discovered, 5'-O-methyldioncophylline D (5). It is the first 7,8'-linked (n-type) naphthylisoquinoline isolated from a Dioncophyllaceae plant. The new alkaloid consists of two closely eluting, slowly interconverting atropodiastereomers, (P)-5 and (M)-5. Their full absolute stereostructures were assigned, i.e., by spectroscopic and online HPLC-CD investigations. (C) 2016 Elsevier Ltd. All rights reserved.