The bacterial replisome is a target for the development of new antibiotics to combat drug resistant strains. The β(2) sliding clamp is an essential component of the replicative machinery, providing a platform for recruitment and function of other replisomal components and ensuring polymerase processivity during DNA replication and repair. A single binding region of the clamp is utilized by its binding partners, which all contain conserved binding motifs. The C-terminal Leu and Phe residues of these motifs are integral to the binding interaction. We acquired three-dimensional structural information on the binding site in β(2) by a study of the binding of modified peptides. Development of a three-dimensional pharmacophore based on the C-terminal dipeptide of the motif enabled identification of compounds that on further development inhibited α-β(2) interaction at low micromolar concentrations. We report the crystal structure of the complex containing one of these inhibitors, a biphenyl oxime, bound to β(2), as a starting point for further inhibitor design.

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N,N-Dialkyl (N′-chlorosulfonyl)chloroformamidines 1 react regiospecifically with hydrazine derivatives to give [1,2,3,5]thiatriazole dioxides. Reaction of 1 with hydroxamic acids and N-methyl hydroxylamine gave derivatives of [1,3,2,4]oxathiadiazole dioxide 7, a new heterocycle.

Oxidative cyclization of benzyltetrahydroisoquinolines has long been considered as a biogenetic route to aporphine alkaloids.2 In 1957, Barton and Cohen3 suggested that phenolic oxidation of diphenolic benzyltetrahydroisoquinoline precursors may generate the bond between the aporphine rings A and D, and this proposal has been amply supported by the results of numerous subsequent biosynthetic and synthetic studies.4'5 We wish to report herewith a second oxidative route, efficient intramolecular coupling of monophen-(1) This investigation was supported by a grant from the National Cancer Institute (CA-12059).(2) R. Robinson, "The Structural Relations of Natural Products," Clarendon, Oxford, 1955, and numerous earlier references cited therein.(3) D. H. R. Barton and T. Cohen in "Festschrift A. Stoll," Birckhauser, Basel, 1957, p 117.

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