苯甲酰胺类抗精神病药物的研究:6β-羟基,乙酰氧基和苯甲酰氧基-3α及β-托品烷衍生物的合成

合成了15个3α和β-取代苯申酰氨基-6β-羟基,乙酰氧基和苯甲酰氧基-托品烷类化合物。其中化合物5d,12c和12d对D-1和D-2受体都有一定的亲和作用。

STUDIES ON THE NEUROLEPTIC BENZAMIDES：SYNTHESIS OF 8β-HYDROXY，ACETOXY AND BENZOYLOXY-3α AND β-TROPANE DERIVATIVES

Fifteen 3α and β-substituted benzamido-6β-hydroxy, acetoxy and benzoyloxy-tropanes were synthesized according to Scheme 1 and Scheme 2. The dey intermediates 3α-amino and3β-amino tropane derivatives 3 and 8 were prepared by reductive amination of tropinone 2 withammonium acetate and sodium cyanoborohydride, and reduction of oxime 7 with sodium respectively.Condensation of 3 and 8 with substituted benzoic acids using 2-bromo-N-methyl-pyridinium iodide ascondensing reagent yielded the corresponding amides 4a～d and 9a～d. Basic hydrolysis of 4a～dfurnished alcohols 5a ～ d. Acid hydrolysis of 9a～d gave alcohols 10a～d.Treatment of 10a withacetic anhydride yielded acetate 11a. Reaction of 10c,d with benzoyl chloride gave the correspondingbenzoates 11c,d. Compounds 5d,12c and 12d exhibited definite affinities to both D-1 and D- 2receptors。