The pH dependences of the rates of hydrolysis of isatin, its N-carboxymethyl derivative and its 5nitro substituted analogues exhibit a complex behaviour, showing a first-and second-order dependence upon hydroxide ion concentration, as well as a pH-independent pathway. The pH dependence is interpreted in terms of the formation of tetrahedral intermediates in different protonic states which may break down to products via hydroxide ion, hydronium ion and water catalysed pathways. These y-lactams are as reactive, or more reactive, than benzylpenicillin.The antibacterial activity of p-lactam antibiotics arises from a combination of their chemical reactivity and their molecular recognition by target enzymes.' One aspect of their chemical reactivity is their acylating power and although, e.g., penicillins, 1, are not very good acylating agents they are more reactive than simple unsubstituted amides.' Since ring strain and reduced amide resonance within the p-lactam has been shown not to contribute significantly to the chemical reactivity of the antibiotic^,^.^ the possibility of non-p-lactam structures showing antibacterial activity has gained ~redibility.~ y-Lactams are obvious candidates for potentially showing similar antibacterial behaviour to that of the P-lactam antibiotics.6 Two important aspects of the acylating power of amides are the activation of the carbonyl group towards nucleophilic attack and the stabilisation of the amine leaving group to facilitate C-N bond fission. Both these requirements are met in isatin (lH-indole-2,3-dione) 2 with the a-carbonyl group both activating the y-lactam carbonyl carbon and stabilising the expelled amine anion, 3. RCONH ExperimentalN-CurboxymethyZisutin.-Isatin (14.7 g, 0.1 mol) was dissolved, with warming, in 2 mol dm-3 sodium hydroxide solution (45 cm3). Chloroacetic acid (14.1 g, 0.15 mol) dissolved in 0.1 mol dm-3 sodium carbonate solution (50 cm3) was added and the solution refluxed for 4 h. Excess concentrated hydrochloric acid was added to precipitate both product and starting material. The precipitate was filtered and stirred with 0.1 mol dm-3 sodium carbonate solution (50 cm3) to extract the product. The solution was filtered and the filtrate was acidified to pH 2 with concentrated hydrochloric acid. The resultant solid was recrystallised from water to give a bright orange powder.

Extracts from culture filtrates of Gibberella fujikuroi grown under various fermentation conditions have yielded the following metabolites : 7-hydroxy-,

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