CONFORMATIONAL ANALYSIS ON ANTICHOLINERGIC DRUG (Ⅰ) MOLECULAR MECHANICS MMPM CALCULATION OF ATROPINE AND OTHER ALKALOIDS IN THE BELLADONNA PLANT

摘要

Alkaloids of balladonna plant were studied by molecular mechanics MMPM calculation. The results showed that the ideal conformation was quite different from the structure found in the crystals of the alkaloids in belladonna plant. The intramolecular hydrogen bond was present between the hydroxy group and carbonyl oxygen atom in the ideal conformation for these alkaloids. The origin of asymmetrical molecules in nature obeys the lowest energy principle. This may be a reason why only S-(-) not R-(+)-isomer, only hyoscyamine not pseudotropine were found to be present in natural belladonna plant, The model of four recognition sites between anticholinergic drug-receptor interaction in mydriasis was suggested, in which the hydroxy group with 8～9 A distanced from nitrogen atom is possibly necessary for maximum mydriasis activity.