R. Epton

Organometallic derivatives of penicillins and cephalosporins a new class of semi-synthetic antibiotics

Abstract Novel semi-synthetic derivatives of penicillin and cephalosporin have been prepared in which the conventional phenyl or heteroaromatic group has been replaced by a ferrocene moiety, and in which the metal atom is in close proximity to the β-lactam ring of the antibiotic; several of the compounds exhibit high antibiotic activity and others are potent β-lactamase inhibitors.

A new class of semi-synthetic antibiotics: ferrocenyl-penicillins and -cephalosporins☆

Abstract A series of ferrocenyl carboxylic acids has been prepared and condensed, via their acid chlorides or in the presence of N , N ′-dicyclohexylcarbodiimide, with both 6-aminopenicillanic acid and 7-aminocephalosporanic acid. Almost all of the ferrocenyl-penicillins and -cephalosporins exhibited antibiotic activity, some being highly active, while others proved to be potent β-lactamase inhibitors.

The synthesis and reactions of homonuclear ferrocene acid anhydrides and their use in the preparation of ferrocenylpenicillins and -cephalosporins☆

Abstract 1,1′-Ferrocenediacetic acid anhydride and O -[1′-(carboxymethylferrocene] benzoic acid anhydride have been prepared and their reactions with amines investigated. These anhydrides have been shown to be useful for the preparation of heteroannularly substituted ferrocenyl-penicillins and -cephalosporins.

Oxidation of ferrocene and some substituted ferrocenes in the presence of horseradish peroxidase

Abstract The enzyme catalysed oxidation of ferrocene and some substituted ferrocenes to the corresponding ferricinium ions by hydrogen peroxide in the presence of native or immobilized horseradish peroxidase has been studied. Initial and maximum rates of oxidation have been determined. It was found that the oxidation was independent of the hydrogen peroxide concentration. The oxidation of ferrocene was effected also by horseradish peroxidase in a coupled system with glucose oxidase in the absence of any added hydrogen peroxide.

The synthesis and reactivity of ferrocenyloxy)-2-tetrahydropyran☆

Abstract Ferrocenylboronic acid was prepared in good yield via the base hydrolysis of ferrocenylboron dibromide. The ferrocenylboronic acid was converted into hydroxyferrocene which was treated with 2,3-dihydropyran to give (ferrocenyl oxy)-2-tetrahydropyran. Lithiation of this pyran gave the corresponding 2-lithiated ferrocene, which was used to prepare some 1,2-disubstituted ferrocenes including 1-carboxy-2-acetoferrocene (“ferrocenyl-aspirin”).

The ferrocene analogues of salicylic acid and aspirin

Abstract The reaction of hydroxyferrocene with 2,3-dihydropyran gave (ferrocenyloxy)-2-tetrahydropyran which on lithiation gave the corresponding 2-lithiated ferrocene which was used to prepare 1-carboxy-2-hydroxyferrocene and 1-carboxy-2acetoferrocene.

Synthesis and characterization of poly(acryloyl morpholine) xerogel networks suitable for the gel permeation chromatography of small molecules

Abstract The synthesis and characterization of a crosslinked poly(acryloyl morpholine) network, Enzacryl® Gel KO, calculated to be effective as a matrix for the g.p.c. of small molecules, is described. Chromatographic performance was evaluated in water, chloroform, dimethylformamide and pyridine. Characteristic g.p.c. behaviour was observed for all standards tested although ‘additional exclusion’ was observed in the case of aliphatic hydrocarbons in the three organic solvents and with aromatic hydrocarbons in chloroform and pyridine. Similar molecular weight fractionation ranges were obtained for poly(ethylene glycols) in the four solvents investigated the molecular weight exclusion limit being less than 1500.

Water-insolubilisation of glycoside hydrolases with cross-linked poly(acryloylaminoacetaldehyde dimethyl acetal) (Enzacryl Polyacetal).

Abstract The preparation of water-insoluble derivatives of alpha-amylase and dextranase by chemical binding with a polyaldehyde derived from cross-linked poly(acryloyl-aminoacetaldehyde dimethyl acetal) (Enzacryl Polyacetal) is described. The water-insoluble derivatives could be used repeatedly against their respective substrates. Bound alpha-amylase and at least a proportion of the bound dextranase molecules were more stable to heat denaturation than are the corresponding free enzymes.

Polymer-supported biopolymer synthesis: 1. High load solid (gel) phase strategy for peptide synthesis with a phenolic poly(acryloylmorpholine)-based support

Abstract An efficient, low-cost, reaction strategy for the solid (gel) phase synthesis of peptides and protected peptide segments has been developed. The strategy involves the use of a new poly(acryloylmorpholine)-based phenolic support matrix, Koch-Light Peptide Resin A. Illustrative syntheses of N -terminal Boc- and Z -protected[Leu]- enkephalin derivatives, including C -terminal acid hydrazides and esters, are described. The strategy, which is effective for the synthesis of peptides at high matrix loadings, is adopted readily for large-scale application.

Soluble polymer-protein conjugates: 1. Reactive N-(sym-trinitroaryl) polyacrylamide/acrylhydrazide copolymers and derived carbonic anhydrase conjugates

Two copolymers of acrylamide and N-acryl-N′-t-butoxycarbonyl hydrazine were prepared and some of the t-butoxycarbonyl groups removed by acid hydrolysis to give acyl hydrazide residues pendant on the hydrocarbon backbone. The modified copolymers were dyed by reaction with sodium trinitrobenzene sulphonate and more acyl hydrazide residues generated by removal of the remaining t-butoxycarbonyl groups. The intense red polymers so produced were activated by treatment with nitrous acid and coupled with carbonic anhydrase to give coloured, water soluble enzyme conjugates. Compared to the native carbonic anhydrase the soluble conjugates were more stable to heat denaturation and exhibited much reduced values of Km when p-nitrophenylacetate was used as substrate.