GB958824A - Improvements in or relating to the production of penicillins - Google Patents

Abstract

An N-(amino substituted) acyl derivative of a 6-aminopenicillanic acid of formula: <FORM:0958824/C2/1> wherein R3 is hydroxy, C1-C6 alkoxy, benzyl or NR4R5 wherein R4 is hydrogen, C1-C6 alkyl, di (C1-C6) alkylamino C1-C6 alkyl, phenyl, benzyl, phenethyl, cyclohexyl or b -morpholinoethyl, R5 is hydrogen, C1-C6 alkyl, benzyl or cyclohexyl, R4 and R5 when taken together are tetramethylene, pentamethylene, -CH2-CH2-O-CH2-CH2 or -CH2-CH2-NH-CH2-CH2, and X is an amino-substituted acyl group having up to 12 carbon atoms having the formula: <FORM:0958824/C2/2> wherein R1 is hydrogen, phenyl, benzyl, phenethyl, alicyclic, indolyl, pyrollidinyl, alkyl or substituted alkyl wherein the substituent is C1-C6 acyloxy, C1-C6 acylmercapto, C1-C6 alkoxy, C1-C6 alkylmercapto, carbobenzoxy, allylmercapto, benzylmercapto, benzyloxy, C1-C6 acylamino, carbobenzoxamido, carboxy or carboxamido, R2 is hydrogen, C1-C6 alkyl, phenyl, cyclohexyl or benzyl, and R6 is a bivalent alkylene radical having from 4 to 6 carbon atoms which, when taken together with the carbon atom to which it is attached, forms a saturated alicyclic ring having from 5 to 7 carbon atoms, is prepared by reacting a solution in a reaction inert solvent, of the N-carboxy anhydride of an amino acid having the formula: <FORM:0958824/C2/3> with a neutral aqueous solution of 6-aminopenicillanic acid, a C1-C6 alkyl ester of 6-aminopenicillanic acid in a reaction-inert solvent, or a 6-aminopenicillanic acid amide in a reaction-inert solvent wherein the amide has the formula: <FORM:0958824/C2/4> at a temperature of from -25 DEG C. to 50 DEG C. and recovering the product therefrom. The Specification describes the production of many penicillins of the above formula such as DL-a -amino-benzylpenicillin, D- and L-a -amino-benzyl-penicillins, the t-butyl ester of aminomethyl penicillin and penicillin amides and of salts formed by neutralizing the appropriate penicillin acid.