title: Alcoholysis of naturally occurring imides: misleading interpretation of antifungal activities.
abstract: The frequent presence of the sulfur-containing amide penangin (10) in leaf extracts of Glycosmis species turned out to be the result of decomposition of imides generated by extraction and storage in MeOH. Reinvestigation of Glycosmis mauritiana and G. cf. puberula with acetone revealed the presence of six imides. In addition to penimides A (1) and B (2) and ritigalin (6), three new derivatives, krabin (4), isokrabin (5), and methoxypenimide B (3), were isolated and identified by spectroscopic methods. All six imides were shown to be susceptible to different rates of methanolic cleavage, leading to their corresponding methyl esters and sulfur-containing amides. Whereas the decomposition products penangin (10), isopenangin (11), and sinharin (14) are known, the corresponding cleavage of methyl N-methylthiocarbamate (7) from ritigalin (6), monitored in situ by (1)H NMR spectroscopy, is described here for the first time. Its structure was further confirmed by GC-MS coupling. HPLC-UV comparison of many different samples of G. mauritiana, extracted with MeOH, revealed considerable chemical variations in sulfur-containing amides, strongly correlated with different antifungal potency. The lack of activity of many methanolic crude extracts can be explained by a preponderance of the inactive decomposition product penangin (10), whereas the corresponding naturally occurring imides penimides A (1) and B (2) and methoxypenimide B (3), extracted with acetone, showed high fungitoxic properties.
authors.affiliation: Comparative and Ecological Phytochemistry, Faculty Center of Botany, University of Vienna, Rennweg 14, A-1030 Wien, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pacher
authors.forename: Adriane
authors.initials: A
authors.lastname: Raninger
authors.forename: Eberhard
authors.initials: E
authors.lastname: Lorbeer
authors.forename: Lothar
authors.initials: L
authors.lastname: Brecker
authors.forename: Paul Pui-Hay
authors.initials: PP
authors.lastname: But
authors.forename: Harald
authors.initials: H
authors.lastname: Greger
mesh_terms: D000438:Alcohols / Q000737:chemistry*; D000935:Antifungal Agents / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D007094:Imides / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D019906:Nuclear Magnetic Resonance, Biomolecular; D027821:Rutaceae / Q000737:chemistry*; D013457:Sulfur Compounds / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000438:Alcohols; D000935:Antifungal Agents; D007094:Imides; D013457:Sulfur Compounds; C552134:penimide A; C552135:penimide B; C552136:ritigalin