| 摘要 |
<p>1416503 Cephalosporins SMITHKLINE CORP 12 June 1973 [14 June 1972 15 Sept 1972 11 May 1973] 27794/73 Heading C2C Novel cephalosporins, having antibacterial activity, of formula wherein M is hydrogen, alkali metal or NH 4 , X is F, Cl or Br and Het is a 5- or 6-membered heterocyclic ring containing carbon and up to four N, O or S atoms, the heterocyclic moiety being substituted with up to 2 C 1 -C 4 alkyl, C 1 -C 4 alkenyl, C 1 -C 4 alkoxy, C 1 -C 4 alkoxy, C 1 -C 4 alkyl, CF 3 , OH, halogen, hydroxy- (C 1 -C 4 )alkyl or SR, R being hydrogen or C 1 -C 4 alkyl, are prepared by acylation of the appropriate 7-amino-3-heterocyclicthiomethyl cephalosporin with a 3-halo-4-hydroxyphenylglycine in which the amino group is protected with a removable protecting group such as t-butoxycarbonyl. Following acylation, the protective group may be removed by trifluoroacetic acid, and the resulting salt converted to the Zwitterionic product by means of a basic ion exchange resin. The compounds of Formula I may also be prepared by displacement of the 3-acetoxy group of a 7- acylated - 3 - acetoxymethylcephalosporin with a suitable mercapto-heterocyclic compound under basic conditions. The preparation of 7-[DL-α-amino-α-(3-fluoro-4-hydroxyphenyl) acetamido] - 3 - (5 - methyl - 1,3,4 - thiadiazol- 2 - ylthiomethyl - 3 - cephem - 4 - carboxylic acid, 7 - [DL -α- amino -α- (3 - fluoro - 4- hydroxyphenyl)acetamido] - 3 - (1 - methyl- 1,2,3,4 - tetrazol - 5 - ylthiomethyl) - 3 - cephem- 4 - carboxylic acid, 7 - [DL -α- amino -α- (3 - fluoro - 4 - hydroxyphenyl)acetamido] - 3- (1,2,3 - triazol - 4 - ylthiomethyl) - 3 - cephem- 4 - carboxylic acid and 7 - [DL -α- amino -α- (3 - chloro - 4 - hydroxyphenyl)acetamido] - 3- (1 - methyl - 1,2,3,4 - tetrazol - 5 - ylthiomethyl)- 3 - cephem - 4 - carboxylic acid is described (Examples 6 to 9). N - t - butoxycarbonyl - 3 - fluoro - 4 - hydroxyphenylglycine is prepared by reacting 3-fluoro - 4-hydroxyphenylglyeine with t-butoxycarbonyl azide in the presence of magnesium oxide. The corresponding 3-chloro and 3-bromo cornpounds are prepared in a similar manner.</p> |
