GB1347979A - Penicillins - Google Patents

Abstract

1347979 Penicillins BEECHAM GROUP Ltd 2 Nov 1971 [12 Nov 1970] 53822/70 Heading C2A The penicillins of Formula I wherein R 1 and R 2 are the same or different and each is alkyl, aralkyl or aryl, R 3 is hydrogen, halogen or an alkyl, aralkyl or an aryl group or R 3 taken together with R 1 completes a carbocyclic ring, and non-toxic salts and esters thereof, have been prepared. Examples of such compounds are D-N-(anilinocarbonylstyren-#<SP>1</SP>- yl) α-amino-p-hydroxybenzylpenicillin, D-N- (α<SP>1</SP> - anilino - carbonylstyren - #<SP>1</SP> - yl) - α- amino - p - hydroxybenzylpenicillin, D - N- [1 - (O<SP>1</SP> - chloroanilinocarbonyl)- propen - 2- yl] - α - amino - p - hydroxybenzylpenicillin and D - N - (1 - anilinocarbonyl - 1 - chloropropen - 2 - yl) - α - amino - p - hydroxy benzyl penicillin and salts and esters of these compounds. A process for the preparation of α- amino - p - hydroxybenzylpenicillin and non- toxic salts and esters thereof comprises hydrolysing an N-protected penicillin of Formula I or a non-toxic salt or ester thereof. In this process the compound of Formula I may be prepared by reacting 6-aminopenicillanic acid or a salt or ester thereof, or the reaction product of 6-aminopenicillanic acid with an organosilicon compound with a derivative of the appropriate carboxylic acid II Suitable derivatives include acid halides, anhydrides or mixed anhydrides. A suitable mixed anhydride may be obtained by treating an alkali metal salt of the acid with an alkyl chlorocarbonate. The carboxylic acid may be prepared by reacting a salt of the D-, L- or racemic α-amino-p-hydroxyphenylacetic acid with a #-diketone of Formula IV: The hydrolysis of the N-protected penicillin may be carried out using an organic or inorganic acid at pH 1-5.