Enantio- or diastereo-selective preparation of valproic acid or valproic acid amide analogs for use as antiepileptic agents, by 4- or 5-stage process using (+)- or (-)-camphor-sultam as chiral auxiliary

摘要

Enantio-selective or diastereo-selective preparation of valproic acid or valproic acid amide analogs (I) involves: (i) N-deprotonating (+)- or (-)-camphor-sultam; (ii) acylating with an acid chloride; (iii) deprotonating the product in the alpha -position and alkylating with an alkyl halide; (iv) saponifying to cleave the camphor-sultam residue; and (v) optionally converting the carboxy group into carboxamide. Enantio-selective or diastereo-selective preparation of valproic acid analogs (I) of formula (IA) or (IB) involves: (i) N-deprotonating (+)- or (-)-camphor-sultam of formula (IIA) or (IIB); (ii) acylating with an acid chloride of formula (III); (iii) deprotonating the product in the alpha -position and alkylating with a halide of formula R-CHR2-X (IV); (iv) saponifying to cleave the camphor-sultam residue; and (v) optionally converting the carboxy group into carboxamide by conventional methods. [Image] R : -CHR1-CH2R7, -C(R8)-CR9R10, -CC-R1 or 3-8C cycloalkyl; Y : OH or NH2; R1-R10H or 1-6C alkyl; and X : halo. - ACTIVITY : Anticonvulsant; Tranquilizer. - MECHANISM OF ACTION : None given.