The molecular structure of 2 alpha-hydroxyneoanisatin and structure-activity relationships among convulsant sesquiterpenes of the seco-prezizaane andpicrotoxane types

The molecular structure of 2 alpha-hydroxyneoanisatin, a positional isomer of the potent neurotoxin anisatin, was determined by X-ray crystallopraphic analysis. This compound and four further seco-prezizaane type sesquiterpen e lactones previously isolated from Illicium floridanum, which represent di fferent structural types with respect to the mode of cyclisation, did not i nduce anisatin/picrotoxinin-like convulsions in mice. Based on these result s and literature data for other seco-prezizaanes, structural requirements f or convulsant activity are discussed. Comparison of the three dimensional m olecular shape and electrostatic properties of active and inactive seco-pre zizaane type lactones with compounds of the picrotoxane type resulted in th e identification of a common pharmacophore structure for these different sk eletal classes of convulsant natural products. (C) 1999 Elsevier Science Lt d. All rights reserved.