Keith Brewster

THE CHEMISTRY OF 1,1′-THIOBIS-(2-CHLOROETHANE) (SULPHUR MUSTARD) PART I. SOME SIMPLE DERIVATIVES

Abstract Some derivatives of 1,1′-thiobis(2-chloroethane) (sulphur mustard) have been synthesised for use as reference compounds in a wide range of studies embracing analysis, metabolism, environmental degradation and decontamination. Compounds include products formed by hydrolysis, substitution and elimination reactions and their oxidised sulphoxide and sulphone analogues. A comprehensive series of methylthio, methylsulphinyl and methylsulphonyl derivatives has been synthesised in support of metabolic studies.

Synthesis of aryl β-D-glucopyranosides and aryl β-D-glucopyranosiduronic acids

Abstract Tetra-O-benzyl-α-D-glucopyranosyl bromide in dichloromethane reacts stereospecifically with solutions of phenols in aqueous sodium or potassium hydroxide, in the presence of phase transfer catalysts, to give good yields of tetra-O-benzyl aryl-β-D-glucopyranosides which are converted into the corresponding aryl β-D-glucopyranosiduronic acids by sequential catalytic debenzylation and catalytic oxidation.

THE CHEMISTRY OF 1,1′-THIOBIS(2-CHLOROETHANE) (SULPHUR MUSTARD) PART II.1 THE SYNTHESIS OF SOME CONJUGATES WITH CYSTEINE, N-ACETYLCYSTEINE AND N-ACETYLCYSTEINE METHYL ESTER

Abstract The syntheses of a number of conjugates of 1,1′-thiobis(2-chloroethane) (“sulphur mustard”) and its simple derivatives with cysteine, N-acetylcysteine and N-acetylcysteine methyl ester are described. These compounds were synthesised for use as reference compounds to support metabolite identification in metabolic studies and, in some cases, to provide standards for analytical procedures being developed for the retrospective confirmation of exposure to sulphur mustard.

Model studies of histrionicotoxin. The synthesis of the 1-azaspiro[5.5]undecane rings system from carbohydrate starting materials

The base-catalysed condensation of nitroethane with dimethyl-t-butylsilyl 2,3-O-isopropylidene-α-D-lyxopentodialdo-1,4-furanoside (2) gives a diastereoisomeric mixture of nitro alcohols, which on desilylation with fluoride ion in tetrahydrofuran rearranges stereospecifically to 1L-[1,2,5/3,4,6(NO2)]-3,4-O-isopropylidene-6-methyl-6-nitrocyclohexane-1,2,3,4,5-pentaol. The analogous condensation of the tetrahydropyranyl ether of 5-nitropentan-1-ol with aldehyde (2) and the subsequent desilylation and rearrangement occur similarly although the degree of stereoselectivity is lower. The major product, 1L-[1,2,5/3,4,6(NO2)]-3,4-O-isopropylidene-6-nitro 6-[4′-(tetra hydropyranyloxy)butyl] cyclohexane -1,2,3,4,5-pentaol (9), is converted into (6S,7R,8R,9R,10R,11S)-7,8,11-tri-o-acetyl-9,10-o-isopropylidene-1-azaspiro[5.5]undecane-7,8,9,10,11-pentaol (13), which has the ring skeleton of histrionicotoxin (1).

Oxidation of some dibenz[b,f][1,4]oxazepines by peracetic acid

A series of variously substituted dibenz[b,f][1,4]oxazepines on treatment with hydrogen peroxide in glacial acetic acid affords the correspondingly substituted 2-(2-hydroxyphenyl)benzoxazole, 10-formylphenoxazine, and dibenz[b,f][1,4]oxazepin-11(10H)-one. An oxaziridine intermediate is implicated as the common precursor of the observed products.

Preparation of the eight monohydroxydibenz[b,f][1,4]oxazepin-11(10H)-ones

The eight possible isomeric monohydroxydibenz[b,f][1,4]oxazepin-11(10H)-ones have been prepared and their mass spectra determined. With the exception of the 7-hydroxy-derivative the fragmentation patterns of the isomers were similar, although the relative line intensities allowed distinctions between the isomers to be made. The syntheses of several irritant monomethoxydibenz[b,f][1,4]oxazepines are also described.