ª‡-amino-substituted penicillins

摘要

The invention relates to a process for the preparation of penicillins of the general formula and non-toxic salts thereof, wherein R is hydrogen, alkyl, aryl, aralkyl, or a heterocyclic group, which may also be substituted, characterized in that 6-aminopenicillanic acid is coupled with the appropriate N-protected amino-substituted carboxylic acid prepared by reacting the amino-substituted carboxylic acid with an aldehyde, and thereafter hydrolysing the N-protected penicillin form, e.g. with dilute mineral acid, to remove the protecting group. The aldehyde is preferably an aromatic or heteroaromatic aldehyde containing an ortho hydroxyl substituent e.g. salicylaldehyde, 5-chlorosalicylaldehyde 3,5 - dichlorosalicylaldehyde, 2 - hydroxy - 1 - naphthaldehyde, and 3 - hydroxypyridine - 4 - aldehyde. It is preferred to react the 6-aminopenicillanic acid with a mixed anhydride prepared by reacting the N-protected amino-substituted carboxylic acid with an ester of chloro-carbonic acid, e.g. ethyl chlorocarbonate. Examples relate to the preparation of a -aminobutylpenicillin, a -aminobenzylpenicillin and a - amino - g - methylthiopropyl penicillin. N - (2 - hydroxy - 1 - naphthylmethylene) - DL-norvaline is prepared by reacting DL-norvaline with 2-hydroxy-1-naphthaldehyde. Sodium N - (2 - hydroxy - 1 - naphthyl - methylene) - a - aminophenylacetate is prepared by reacting sodium a -amino-phenylacetate with 2-hydroxy-1-naphthaldehyde. N - (2 - hydroxy - 1 - naphthyl methylene) - DL-methionine is prepared by treating DL-methionine with 2-hydroxy-1-naphthaldehyde. Sodium N-salicylidene a -aminophenyl acetate is prepared by treating sodium a -aminophenyl acetate with salicylaldehyde. Sodium N - (5 - chlorosalicylidene) - a - aminophenyl acetate is prepared by treating sodium a -aminophenyl acetate with 5-chlorosalicylaldehyde. N - (3,5 - dichlorosalicylidene) - DL - norvaline is prepared by treating DL-norvaline with 3,5-dichlorosalicyl aldehyde.