GB1267936A - DERIVATIVES OF alpha-AMINOPENICILLINS - Google Patents

Abstract

1,267,936. Derivatives of α-amino penicillins. BEECHAM GROUP Ltd. 26 May, 1970 [28 May, 1969; 7 April, 1970], Nos. 26898/69 and 16292/70. Heading C2A. α-Aminopenicillin derivatives of the general formulµ where R is an alkyl, cycloalkyl, alkenyl, cycloalkenyl, aralkyl, aryl or heterocyclic group which may be substituted, and where in (I) X is NH 2 , optionally in the form of an acid addition salt, or a protected amino group of the general formulae or tautomeric modifications thereof, wherein the dotted lines represent hydrogen bonds, R<SP>1</SP> is C 1-6 alkyl, R<SP>2</SP> is either H or together with R<SP>1</SP> completes a carbocyclic ring, R is C 1-6 alkyl or alkoxy, and Z represents the residue of a substituted or unsubstituted benzene or naphthalene ring, may be prepared (a) by reacting a salt of a penicillanic acid of formulae with an acyloxymethyl compound of formula Y.CH 2 O.COR, wherein Y is Br or Cl, in an organic solvent which may optionally contain a small amount of water or (b) by reacting an acyloxymethyl-6-aminopenicillanate of formula with a carboxyl activated derivative of a carboxylic acid of formula wherein M represents an amino group, a protected amino group or a group which may subsequently be converted to an amino group, and then when M is not an amino group or a group of Formula III or IV, converting it to such a group. The phenolic hydroxyl group in the carboxy activated derivative of the acid of Formula IX may be protected during the reaction with the acyloxymethyl 6-aminopenicillanate, and the protecting group is subsequently removed. Preferaby M is an amino group protected by protonation or with a benzyloxycarbonyl group or is an azido group. The carboxyl activated derivative of the carboxylic acid of Formula IX may be a halide, anhydride or mixed anhydride. Specified derivatives include pivaloyloxymethyl 6 - [(-) α - amino - α - (p - hydroxyphenyl)- acetamido] penicillanate, pivaloyloxymethyl 6 - [2,2 - dimethyl - 5 - oxo - 4 - (p - hydroxyphenyl) - 1 - imidazolidinyl] penicillanate, acetoxymethyl 6 (-) α - amino - α - (p - hydroxyphenyl) acetamido] penicillanate and acetoxymethyl 6 [2,2 - dimethyl - 5 - oxo - 4 - (phydroxyphenyl) - 1 - imidazolidinyl] penicillanate. The above α-aminopenicillin derivatives of the general Formulµ I and II are active against Gram-positive and Gram-negative bacteria and are useful as antibacterial agents, nutritional supplements in animal foods and as therapeutic agents in the treatment of mastitis.