Peter G. Sammes

Penicillinase active sites: Labelling of serine-44 in β-lactamase I by 6β-bromopenicillanic acid

fi-Lactamases inactivate penicillins and cephalosporins by catalysing the hydrolysis of the P-lactamase ring in these ~lini~~ly-v~uable antibiotics. The resistance of pathogenic bacteria is frequently due to their production of p-lactamases. Yet we know little in chemical terms about catalysis by these enzymes, Until now, affinity labelling has not been carried to a successful conclusion with any fl-lactamase. @-Lactamase I from ~~~~~u~ cereus has been used here ; it is readily prepared [l], the sequence has been studied [2], it is homologous with the enzymes from pathogens whose structure is known [3], and it is being examined crystallographically [4f. The reagent used here for affinity labelling, 6~.bromopeni~ill~ic acid, inactivates &lactamase I in a rapid, stoicheiometric reaction IS], and the rate of inactivation is decreased by the presence of substrate [6]. We now report that the site labelled is serine44. This result invites us to regard certain /3-lactamases as serine enzymes.

On the acid catalysed isomerisation of some substituted spirobenzopyrans

Abstract Upon treatment of photochromic spirobenzopyrans with trifluoroacetic acid in non-protic solvents, acid-catalysed ring opening occurs to form thee protonated merocyanine, which, upon quenching with base, allows formation of the coloured merocyanine by a non-thermal, non-photochemical route.

Steric acceleration of intramolecular cycloaddition reactions

Abstract Use of conformational constraints, induced by different ortho -substituents in 1-allyloxy-2-(substituted)methylbenzenes, where the substituent is a 1,3-dipole such as the azide or 3-oxidopyridinium group, can be employed to accelerate the 1,3-dipolar cycloaddition reaction. In this manner cycloadditions that otherwise do not proceed can be forced to react.

Substituent tuning of photoreversible lithium chelating agents

Strategically placed substituents on crowned indolospirobenzopyran rings can be used to tune their chelating ability in order to obtain photoreversible lithium binding agents.

Preparation of some new intercalating europium(III) sensitizers

The synthesis of phenanthridinium salts linked to a chelating phenanthroline-2,9-dicarboxylic acid group, as in 1 and 2, is described. These derivatives behave as useful probes for the identification of DNA single strands in a new homogeneous assay.

Anion effects on the luminescence of europium complexes

Anions such as fluoride and phosphate, both known to be able to coordinate to lanthanide ions, can compete with water in luminescent europium complexes, involving a sensitizer and shielding ligand, hence, in some cases, affecting the luminescent behaviour of these complexes in aqueous solution.

Some studies on peptide analogues involving the sulphinamide group

The title compounds are of interest as possible transition state inhibitors of peptidases. A route to N(alkylsulphinyl)amino acids is described. A method for generating α-benzamidosulphinamides is reported; a general route to such systems failed owing to the difficulty of removing the protecting group and the apparent instability of α-amino sulphinamides. A crystal structure on the N-phthalimido-protected α-sulphinamide 16a showed the tetrahedral disposition of substituents around the sulphur atom and the deviation from planarity about the sulphinamide nitrogen atom.

The trityl group as a removable steric buttress in cycloaddition reactions

The trityl group is utilised as an effective, temporary, steric buttress in an intramolecular Diels–Alder reaction between an alkene and furan ring.

Use of steric buttresses to enhance intramolecular cycloadditions

Examples are given illustrating the use of ortho-substituents on substituted benzene rings as steric buttresses to limit the conformational space available to a dipole and dipolarophile, forcing them into closer proximity and hence to allow cycloadditions to proceed that otherwise do not.

On the preparation and rearrangement of some vinylic sulphoxides

The condensation of methyl benzenesulphinylacetate 1 with a series of aldehydes has been explored using different catalysts. With zinc chloride, the enolate of 1 produces the conjugated ester directly. A base-catalysed rearrangement of these conjugated esters to the corresponding γ-hydroxy unsaturated ester can be effected. Alternatively, the use of magnesium methoxide as catalyst during the condensation of the aldehydes with the reagent 1 produces these hydroxy esters directly.