Method for the total synthesis of a category of chemical derivatives having a papaverolinic structure

摘要

A substituted papaveroline of the formula FORM:1086953/C2/1 is prepared by condensing 1,2-di-(benzoyloxy)-4-(chloroformylmethyl)benzene with an amine of the formula FORM:1086953/C2/2 in the presence of aluminium chloride to form an amide of the formula FORM:1086953/C2/3 reducing the amide with sodium amalgam to form an amide of the formula FORM:1086953/C2/4 and dehydrating the latter amide with phosphorus pentoxide. A brominated benzoyl-papaveroline is prepared by brominating a substituted papaveroline of the first formula above or by brominating papaveroline and the forming the tetrabenzoyloxy structure. The Specification also refers to a synthesis similar to that used for the preparation of the substituted papaveroline of the first formula above but using as reactants an amine and a chloroformylmethyl compound of the respective formulae FORM:1086953/C2/5 An amine of the above formula is prepared by benzoylating catechol, subjecting the resulting 1,2-dibenzoyloxy-benzene to a Friedel-Crafts reaction with acetyl chloride, treating the resulting 3,4-dibenzoyloxy-acetophenone with sodium nitrite and glacial acetic acid, and reducing the resulting nitroso compound of the formula FORM:1086953/C2/6 1,2 - Dibenzoyloxy - 4 - chloroformylmethylbenzene is prepared by oxidizing 1,2-dibenzoyloxy-4-methylbenzene with potassium permanganate in acid solution, treating the resulting 1,2-dibenzoyloxy-benzaldehyde with potassium cyanide, hydrolysing the resulting cyano compound of the formula FORM:1086953/C2/7 reducing the resulting 1,2-dibenzoyloxy-4-(1-hydroxy -1 - carboxymethyl) - benzene with hydrogen and treating the resulting 1,2-dibenzoyloxy-4-carboxymethylbenzene with thionyl chloride.