Chiral capillary electrophoresis of the methaqualone rotamers: Indication of a stereoselective metabolism
JOURNAL OF MICROCOLUMN SEPARATIONS
Authors: Zaugg, S; Thormann, W
Abstract
Methaqualone (MQ, 2-methyl-3-o-tolylquinazolin-4(3H)-one) is a hypnotic and anticonvulsive drug in which the rotation about the nitrogen-to-aryl bond between the planar 2-methyl-quinazolin-4(3H)-one structure and the o-tolyl moiety is sterically hindered. MQ is thus a chiral substance whose enantiomers are shown to be separable by acidic chiral capillary electrophoresis (CE) in presence of (2-hydroxypropyl)-beta -cyclodextrin (OHP-beta -CD). Using a pH 2.5 phosphate buffer containing 8 mM OHP-beta -CD, chiral discrimination is possible up to an intracapillary temperature of at least 70 degreesC. For a given capillary length, optimized separation is attained at the lowest running temperature. CE is demonstrated to be a simple and an attractive approach for analysis of MQ enantiomers in alkaline extracts of urines that were collected after single-dose administration of a tablet containing 250 mg MQ. Electropherograms obtained with urines collected at different time intervals after drug intake reveal that the size ratio of the two peaks allocated to MQ is changing with time, thus indicating the existence of a stereoselective metabolism of that drug. For unambiguous elucidation of the stereoselectivity, however, chiral analyses of urinary MQ metabolites will have to be undertaken. (C) 2001 John Wiley & Sons, Inc.
Dictyoquinazols A, B, and C, new neuroprotective compounds from the mushroom Dictyophora indusiata
JOURNAL OF NATURAL PRODUCTS
Authors: Lee, IK; Yun, BS; Han, G; Cho, DH; Kim, YH; Yoo, ID
Abstract
In an effort to identify neuroprotective compounds against excitatory neurotoxins from edible and medicinal mushrooms, dictyoquinazols A (1), B (2), and C (3) have been isolated from the methanolic extract of the mushroom Dictyophora indusiata. On the basis of NMR studies, their structures have been assigned as unique quinazoline compounds, which are very rare in nature. 2 and 3 existed as mixtures of rotamers (2a, 2b and 3a, 3b) inseparable by HPLC because of fast interconversion. The E/Z isomers of these compounds were assigned by comparison of H-1 NMR, C-13 NMR, and NOESY spectra and by (3)J(C,H) coupling constants. Dictyoquinazols protected primary cultured mouse cortical neurons from glutamate- and NMDA-induced excitotoxicities in a dose-dependent manner.