W. Martin Owton

tert-Butyl 3-Carboxyethyl-3-phosphonodiethylpropionate. A Novel Reagent for Stobbe-Like Condensations

Abstract tert-Butyl-3-carboxyethyl-3-phosphonodiethylpropionate was prepared and reacted with a range of aldehydes to give, after hydrolysis, itaconic half esters.

Synthesis of 6/7-Halotetralones

Abstract The title compounds were prepared from halobromobenzenes via a palladium catalysed coupling followed by cyclisation.

Novel immunosuppressive butenamides

2-[4-(1,1-Dimethylethyl)phenyl]thiophene 12 was carboxylated using butyllithium and carbon dioxide to give 5-[4-(1,1-dimethylethyl)phenyl]thiophene-2-carboxylic acid 13. Conversion of the acid 13 using diphenyl phosphazidate and triethylamine gave 5-[4-(1,1-dimethylethyl)phenyl]thiophene-2-carbonyl azide 14, which was rearranged in toluene at 110 °C with loss of nitrogen to give the isocyanate 15; this in turn was treated with sodium 1-cyanoprop-1-ene 2-oxide 16 in tetrahydrofuran to give 2-cyano-N-{5-[4-(1,1-dimethylethyl)phenyl]thiophen-2-yl}-3-hydroxybut-2-enamide 17. Analogous chemistry has been utilised to synthesize both phenylheteroarylbutenamides and phenylbutenamides which display immunosuppressive activity towards proliferating concanavalin A-stimulated T-lymphocytes.

A new synthesis of Rhein

Abstract A novel synthesis of Rhein ( 2 ), the active metabolite of the anti-osteoarthritic drug Diacetyl Rhein ( 1 ) has been acehived. Key steps include stereospecific olefination of aldehyde 21 with novel phosphonate 28 and the cyclisation of acid 31 to produce anthracene 32 .

Direct fluorination of the anthraquinone nucleus: scope and application to the synthesis of novel rhein analogues

Abstract Direct fluorination of the functionalised anthraquinone dimethyl rhein methyl ester with Selectfluor TM proceeds regioselectively, providing a concise approach to fluorinated compounds of potential medicinal interest. This represents a new use for Selectfluor TM which hitherto has only been used for fluorinating relatively activated compounds.

Additions to alkenes via metal ion-promoted oxidation of 2,2′-dipyridyl disulphide and bis-(2-aminophenyl) disulphide

Vicinal trifluoroacetoxysulphides, which readily afford vicinal hydroxysulphides, are obtained by oxidative addition of 2,2′-dipyridyl disulphide and of bis-(2-aminophenyl) disulphide to alkenes in dichloromethane–trifluoroacetic acid promoted by copper(II) acetate.

Synthesis Of 5-tert-Butyl Benzo[b]thiophene-2-carboxylic Acid

Abstract The title compound was prepared from 4-tert-butyl cyclohexanone in high yield by a simple three step procedure.

Synthesis of 4,5,8-trimethoxy-9,10-dioxo-9,10-dihydroanthracene-2-carboxylic acid, an analogue of rhein with improved systemic exposure in the guinea pig

N,N-Diethyl(2-methoxy-4-methyl)benzamide 4 has been lithiated and treated with 2,5-dimethoxybenz-aldehyde to give 3-(2′,5′-dimethoxyphenyl)-7-methoxy-5-methylisobenzofuran-1(3H)-one 5. Reduction and cyclisation gives 4,5,8-trimethoxy-2-methylanthracen-10-ol 7 which is oxidised to give 4,5,8-trimethoxy-2-methylanthraquinone 8. Demethylation gives the natural product helminthosporin 9, oxidation gives 4,5,8-trimethoxy-9,10-dioxo-9,10-dihydroanthracene-2-carboxylic acid an analogue of the osteoarthritis drug rhein. Alternatively, dimethylrhein methyl ester 12 may be iodinated and the iodine displaced with methoxide to provide a large-scale synthesis of 3. Plasma concentration data in the guinea pig were obtained for 3, diacetylrhein, dimethylrhein and 4,5-dimethyl-8-fluororhein after oral dosing.

Anthraquinones related to rhein inhibit glucose uptake into chondrocytes. A mechanism for anti-osteoarthritis drugs?

Abstract Rhein has been shown to inhibit the uptake of glucose into Ehrlich Ascites tumor cells. In this paper we show that a wide range of antrhaquinones related to rhein can also inhibit glucose uptake into chondrocytes, many significantly more than the parent molecule.

Additions to alkenes via metal ion-promoted oxidation of dialkyl and diaryl disulphides

Reactions of alkenes with di-n-propyl, diphenyl, and dibenzyl disulphide in the presence of lead(IV) salts in trifluoroacetic acid-dichloromethane are described. The products, vicinal trifluoroacetoxy-sulphides, are obtained in higher yields with manganese (III) salts as the oxidant. Alternative reaction conditions with use of iron(III) salts or in the absence of added metal salts are also described. Trifluoroacetoxysulphides derived from diphenyl disulphide react with acetonitrile under Ritter conditions to give acetamidosulphides but trifluoroacetoxysulphides derived from dibenzyl disulphide only give the vicinal acetamidosulphides in poor yield as a result of an alternative reaction pathway affording benzylacetamide. Conversions of acetamidosulphides into aminosulphides and into acetamidothiols are described.