Extract screening by HPLC coupled to MS-MS, NMR, and CD: a dimeric and three monomeric naphthylisoquinoline alkaloids from Ancistrocladus griffithii.
Three new monomeric naphthylisoquinoline alkaloids, ancistrogriffines A, B, and C, and the first dimer of a 7,8'-coupled naphthylisoquinoline, ancistrogriffithine A, have been detected by phytochemical online screening of plant extracts of Ancistrocladus griffithii, using the analytical 'triad' HPLC-MS/MS, HPLC-NMR, and HPLC-CD. Ancistrogriffithine A, as well as ancistrogriffines A and C, were structurally completely assigned (including the absolute configuration) right from the extract, without previous isolation. Furthermore, two related, but known alkaloids, ancistrocladine and hamatine, were identified. Except for ancistrogriffine B, which occurs in trace quantities only, all new alkaloids were then isolated preparatively and the initial assignments were fully confirmed by conventional offline methods. Of particular interest is the constitutionally and configurationally unprecedented structure of ancistrogriffithine A, which is simultaneously the first dimeric naphthylisoquinoline alkaloid from an Asian Ancistrocladus species. Ancistrogriffithine A and ancistrogriffine A are active against Plasmodium falciparum. Furthermore, the latter compound shows good activity against Leishmania donovani. The results demonstrate the ability of modern online methods like HPLC-NMR, -MS/MS, and -CD to serve as powerful tools for the reliable structural elucidation of even complex structures of trace compounds in crude biological matrices.
Bringmann
Gerhard
G
Institute of Organic Chemistry, University of Würzburg, Am Hubland, D-97074, Würzburg, Germany. bringman@chemie.uni-wuerzburg.de
Wohlfarth
Michael
M
Rischer
Heiko
H
Schlauer
Jan
J
Brun
Reto
R
D000470:Alkaloids / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000981:Antiprotozoal Agents / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002942:Circular Dichroism; D007893:Leishmania donovani / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D019684:Magnoliopsida / Q000737:chemistry*; D013058:Mass Spectrometry; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry; D010963:Plasmodium falciparum / Q000187:drug effects; D014345:Trypanosoma / Q000187:drug effects
D000470:Alkaloids; D000981:Antiprotozoal Agents; D010936:Plant Extracts