GB1327270A - Acylation of 6-aminopenicillanic acid and 7-aminocephalospor anic acids - Google Patents

Abstract

1327270 Substituted penicillins and cephalosporins OSAKA UNIVERSITY PRESIDENT OF 26 Oct 1970 50674/70 Heading C2A A process for producing a 6-aminoacylamidopenicillanic acid VI wherein H 2 N-R-CO- is an amino acid residue, R is alkylene or the grouping IX R 5 is H, Me or MeS- and R 6 is alkyl alkylthio, aryl, arylthio, arylalkyl, aryloxy or a heterocyclic group or R 5 and R 6 together form a substituted or unsubstituted ring structure such as cycloalkyl or a heterocyclic group, or a non-toxic salt thereof or a 7-aminoarylamidocephalosporanic acid VII wherein X is hydrogen, acetoxy or -S-Y, where Y is alkyl, alkenyl or nucleophilic group, or a non-toxic salt thereof, which comprises acylating respectively 6-amino-penicillanic acid or a derivative thereof, or a 7-amino-cephalosporanic acid or a derivative thereof, with an N-protected amino acid III wherein R 1 and R 2 are each C 1 -C 3 alkyl groups or R 1 and R 2 together form a piperidine ring or a morpholine ring and R 3 is a C 1 -C 3 alkyl group, R 4 is hydrogen or a C 1 -C 3 alkyl group or R 3 and R 4 together form a cyclopentyl or cyclohexyl ring, or with a functional acid derivative thereof, to form an N-protected 6-aminoacylamidopencillanic acid of the Formula IV wherein R, R 1 , R 2 , R 3 and R 4 are as defined above, or are an N-protected 7-aminoacylamidocephalosporanic acid of the Formula V wherein R, R 1 , R 2 , R 3 , R 4 and X have the meanings defined above, and then hydrolysing the N-protected 6-aminoacylamidopenicillanic acid or a salt thereof, or an N-protected 7- aminoacylamidocephalosporanic acid or a salt thereof. The 6-aminopenicillanic acid or 7- aminocephalosporanic acid may be reacted with a mixed acid anhydride obtained by treating a salt of an N-protected amino acid with a substituted acetic acid halide or alkyl chloroformate in the presence of a small amount of catalyst, e.g. a tertiary base of Formula VIII R 7 and R 8 may be the same or different and each represents a C 1 -C 3 alkyl group, benzyl group or R 7 and R 8 together with the nitrogen atom represent a morpholine or piperidino group. Hydrolysis may be carried out with a diluted mineral acid or a strong organic acid. The compounds and intermediates of the process are in many cases novel. Pharmaceutical compositions having antibiotic properties may be prepared using the antibiotics according to the invention as active ingredients.