GB1303491A - - Google Patents

Abstract

1303491 Penicillin esters LOVENS KEMISKE FABRIK PRODUKTIONSAKTIESELSKAB 19 April 1971 .[24 March 1970] 14303/70 Heading C2A Novel penicillin esters of Formula I and salts thereof, wherein R<SP>1</SP>CO is the 6-acylating side chain of a known penicillin having a basic group on its said side chain and R<SP>2</SP>CO is the 6-acylating group of a known penicillin not having a basic group in its said side chain are prepared by either (a) reacting a base salt of an R<SP>1</SP>CO - amino - penicillanic acid (wherein the basic group on the R<SP>1</SP>radical may be replaced by a group Z which is easily convertible to the said basic group) with a compound of formula YCH 2 Cl where Y is bromine, iodine, an alkylsulphonyl group or an aryl sulphonyl group, to give the corresponding penicillin chloromethyl ester which is reacted with a base salt of an R<SP>2</SP>CO-aminopenicillanic acid, and if necessary converting the group Z to the required basic group; or (b) proceeding as in (a) except that the acylamino-penicillanic acids are interchanged; or (c) replacing one or both acylaminopenicillanic acids by 6-amino-penicillanic acid to give a compound wherein one or both of the RCO groups in Formula I are replaced by hydrogen, and N-acylating this compound to provide the required R<SP>1</SP>CO- and/or R<SP>2</SP>CO.groups. The basic group may be an amino, substituted amino or guanyl-ureido group. The group Z which may replace it may be protected-amino or an NO 2 , Cl or azido group. Procedure (c) above may be conducted by simply reacting 6- aminopenicillanic acid with a compound of formula YCH 2 Y<SP>1</SP>where Y is as before and Y<SP>1</SP> is Cl, Br, I, or alkyl- or aryl-sulphonyloxy, when a compound wherein both RCO groups in Formula I are replaced by H, i.e. bis(6-aminopenicillanoyloxy).methone is obtained, this compound being a novel intermediate. Other novel intermediates are 6#-(D-α- azido - α - phenylacetamido) - penicillanoyloxymethyl esters of phenoxymethylpenicillin, benzylpenicillin, 5 - methyl - 3 - phenyl - 4- isoxazolylpenicillin, and 3 - (o - chloropehnyl)- 5-methyl-4-isoxazolylpenicillin. Pharmaceutical compositions having antibiotic activity comprise a penicillin ester of Formula I or a non-toxic salt thereof together with a pharmaceutically acceptable carrier.