Stephen James Dr Ray

Novel antifungal 2-aryl-1-(1H-1,2,4-triazol-1-yl)butan-2-ol derivatives with high activity against aspergillus fumigatus.

Abstract Replacement of one triazole ring of fluconazole with 4-pyridinyl leads to an increase in activity against Aspergillus fumigatus. Introduction of an α-methyl group has a marked additional beneficial effect. Investigation of pyridinyl and pyrimidinyl analogues resulted in the identification of 30 (UK-109, 496, voriconazole) which has excellent potency against a broad range of fungal pathogens including A. fumigatus and Candida krusei.

Transformation of cephalosporins: preparation of a 3-methyl-3-nitro-4-hydroxyiminocepham

The reaction of N2O3 with 3-methyl-7β-phenoxyacetamidoceph-3-em-4-carboxylic acid gives, by an addition–decarboxylation sequence, 3α-methyl-3β-nitro-4(E)-hydroxyimino-7β-phenoxyacetamidocepham-4carboxylic acid.

Transformation of cephalosporins: a new reaction with dinitrogen trioxide

The reaction of N2O3 with 2,2,2-trichloroethyl 3-methyl-7β-phenoxyacetamidoceph-3-em-4-carboxylate gives by a new reaction mode, 2,2,2-trichloroethyl 4α-hydroxy-3α-methyl-3β-nitro-7β-phenoxyacetamidocepham-4-carboxylate, the structure and stereochemistry of which were elucidated by 400 MHz n.m.r. and difference nuclear Overhauser enhancement spectroscopy.

Transformations of cephalosporanates: the formation of 4-alkoxyformamidoceph-2- and -3-ems

A ceph-3-emcarboxylic acid reacted with diphenylphosphoryl azide–toluene–t-butyl alcohol–triethylamine to give the 4α- and 4β-t-butoxycarbonylceph-2-ems and a 4-t-butoxyformamidoceph-2-em. Interconversion studies on the 4α- and 4β-esters were performed. Reaction in the presence of excess of sodium azide gave as the sole β-lactam product a 4-t-butoxyformamidoceph-3-em.