Diesters of 18-hydroxy-yohimbane-carboxylic acids

摘要

Novel compounds of the formula wherein R1 is a C1- 3 alkyl radical, R2 and R3, which may be the same or different, are H, alkyl (which may be joined together to form a ring) or aryl, which may be substituted by one, two or three C1- 3 alkoxy radicals, and R4 is CH3O- or H, and their salts with inorganic and organic acids, and their optically active isomers, are prepared by reacting a compound of formula wherein R1 and R4 are as previously defined, in a known manner with a reactive carboxylic derivative of an a -hydroxy acid of formula wherein R2 and R3 are as previously defined, and X is a protective group, and the protective group in the resulting reserpic acid derivative is split off, whereupon the desired product obtained is, if desired, converted into a salt with an organic or inorganic acid, and/or separated into its optically active isomers. The compounds are of use in the pharmacological field. 18 - (O - tetrahydropyranyl - DL - mandelic acid) ester of methyl reserpate, which may optionally bear up to three CH3O- groups on the mandelic acid benzene ring, and 18-(a -tetrahydropyranyloxy - cyclohexane - carboxylic acid) ester of methyl reserpate are isolated reserpic acid derivatives, as intermediates in the above process. The imidazolide of O-tetrahydropyranyl-DL-(and L)-mandelic acid and also the 3,4-dimethoxy and 3,4,5-trimethoxy DL-derivatives thereof are prepared by reacting the corresponding mandelic acid with dihydropyran in the presence of p-toluene sulphonic acid to give the corresponding tetrahydropyranyl ester of O-tetrahydropyranyl mandelic acid, which is then reacted with NaOH to give the Na-salt of the O-tetrahydropyranyl mandelic acid, followed by acidification to the free acid, with oxalic acid, which is then reacted with N,N1-carbonyldiimidazole to give the imidazolide. The imidazolide of a -tetrahydropyranyloxy-cyclohexane-carboxylic acid is prepared by reacting cyclohexanone cyanohydrin with dihydropyran to give a -tetrahydropyranyloxy-cyclohexane-carboxylic acid nitrile, which is then subjected to alkaline saponification, yielding the free acid, which is subsequently reacted with N, N1-carbonyldiimidazole.