Angela W. Guest

6-Spirocyclopropyl penems

Abstract 6-Alkylidene penems were found to react with diazomethane to give pyrazolines, which were thermolysed to afford the title compounds.

Preparation and properties of 7α-formamido cephalosporins

The preparation of novel antibacterially active 7α-formamido cephalosporins from the corresponding 7α-(methylthio) analogues by mercury (II)-mediated displacement with ammonia and subsequent formylation is described. The amine (2), a versatile intermediate, was prepared and acylated to give a wider range of 7α-formamido cephalosporins. Modifications at C-3 are discussed, in particular the preparation of the 3-(heterocyclylthiomethyl) cephalosporin (44) and the 3-(pyridylmethyl) derivative (49).

6α-fluoroalkyl penicillins

Abstract Fluorination of the protected 6α-(hydroxymethyl) amine (19), deprotection and acylation afforded the fluoromethyl penicillin (8). Similar reaction with the 6α-formyl penam (13) proceeded only to the intermediate fluorohydrin (14).

6α-(N-substituted formamido) penicillins and derivatives

Abstract A simple N -substituted formamido penicillin was found to differ in rate and mode of decomposition from its unsubstituted counterpart. A series of derivatives were prepared and their antibacterial properties examined.

Degradation of BRL 36650, a 6α-formamido penicillin: C(5)–C(6) bond cleavage

Under mildly acidic aqueous conditions, a 6α-formamido penicillin has been found to degrade with cleavage of the C(5)–C(6) bond as the prinicpal route; more extreme acidic or basic conditions gave other degradation products, which were also charcterised.

Aqueous and anhydrous degradations of 6α-formamidopenicillins

When an aqueous solution of the 6α-formamidopenicillin BRL 36650 (1) was set aside for 36 h, an essentially quantitative C(5)–C(6) cleavage resulted, yielding the α,α-bis(acylamino) acid (6) and N-formylpenicillamine (10). The unsubstituted phenyl compound (2) behaved analogously, but the 4-aminophenyl derivative (3) showed five-fold greater aqueous stability. Over a wider range of pH, the penicillin (1) was converted into the penillic acid (21) and/or the penicilloic acid (22) at 1 < pH < 7 and into the piperazine ring-opened diacid (23) at pH 10.Both the 6β-aminopenicillin ester (15) and the urethane (24) yielded penicilloates (25) and (26) on base-catalysed methanolysis. However, while (15) was recovered in good yield after prolonged treatment with triethylamine, (24) underwent C(5)–C(6) cleavage, forming the dihydrothiazole (27). These results are interpreted in terms of initial oxazolone formation via the 6β-amido substituent, followed by C(5)–C(6) bond breaking.