David A. Widdowson

New synthesis of diaryliodonium sulfonates from arylboronic acids

Abstract Diaryliodonium salts, precursors to [ 18 F]fluoroaromatics, have been prepared, in a regioselective manner, from readily available arylboronic acids eliminating the need for acid sensitive and toxic organotin intermediates.

Transition metal mediated thiation of aromatic rings

Abstract Three approaches to aromatic thiation have been studied. Dependent upon access to the necessary starting material, displacement of halogen in haloarenetricarbonylchromium(0) complexes by nucleophilic sulphur, quenching of lithiated arenetricarbonylchromium(0) complexes by electrophilic sulphur or palladium catalysed cross coupling of aryl iodides with alkylthiotrialkylstannanes were all effective and apparently general in scope. The latter is the preferred process.

Unsymmetrical biaryl synthesis: an approach to natural highly functionalised biaryls via palladium catalysed coupling

Abstract The synthetic utility of the palladium catalysed cross-coupling reaction of aryl iodides and bromides with aryl Grignard reagents has been explored with respect to the polyoxygenated and polyalkylated arenes found in nature. High yields of unsymmetrical biaryls are obtained, free of symmetrical byproducts. The method will tolerate a limit of two ortho -substituents in the biaryl system with a preference for the 2 groups to be on the arylmagnesium ring. Transition state models of the potential rate determining steps are discussed with respect to this preference.

Sterol mutants ofSaccharomyces cerevisiae: Chromatographic analyses

The sterols accumulated by ergosterol deficient mutants of the geneserg6, erg2, erg3, anderg5 (formerlypo11, po12, po13, andpo15) have been analyzed by gas liquid chromatography. Together with pure sterols obtained from the mutants, they were characterized on SE-30, OV-17, and OV-225. The effects of molecular structure on the retention characteristics of a range of C28 ergostane sterols have been studied. The double mutants obtained by crossing the single mutants were also analyzed and their sterols identified where possible. The effects of theerg mutations on the control of sterol biosynthesis in yeast are discussed.

Biosynthesis of terpenes and steroids: VII. Unified scheme for the biosynthesis of ergosterol in Saccharomyces cerevisiae☆

Abstract Feeding experiments with labelled sterols support a proposed scheme for ergosterol biosynthesis. Some non-natural sterols have been found to be incorporated into ergosterol and the possible significance of these results is discussed.

The synthesis of 4 - Substituted Indoles via arenetricarbonylchromium(0) complexes

Abstract Lithiation of tricarbonyl-η 6 -(1-tri-isopropyisilylindote)chromium(0) and η 6 -(1 -tri-isopropylsilyl-3-methoxymethylindole)tricarbonylchromium(0) followed by an electrophilic quench produced a series of 4-substituted indole complexes. For the 4-acyl, -allyl and -alkenyl analogues, transmetallation of the lithio- species to the corresponding cupro- complexes and reaction with the appropriate halides (in the alkenyl case with palladium catalysis) gave in total, a wide range of 4-substitutents. The complexes were decomplexed and desilylated to produce the 4-substituted indoles in moderate to good overall yield.

Transition metal mediated organic synthesis: the synthesis of moracin M

Abstract The Palladium catalysed cross coupling of 2-halo- or metallo-benzofurans with both 5-metallo- or halo-resorcinol tricarbonyl chromium(O) complexes and the uncomplexed resorcinols, has been evaluated and in consequence, moracin M has been synthesised in good yield by the cross coupling of 6-(t-butyldiphenylsiloxy)-2-trimethylstannylbenzofuran with 5-iodoresorcinolbis(triisopropylsilyl) ether and fluoride ion deprotection of the product.

New developments in palladium catalysed cross coupling: the coupling of alkyl iodides with alkyl Grignard reagents

Abstract The species generated by the in situ reduction of 1,1′-bis(di-phenylphosphino)ferrocenepalladium dichloride is an effective catalyst for the cross coupling of alkyl iodides with alkyl Grignard reagents.

Biosynthesis of terpenes and steroids. Part IX. The sterols of some mutant yeasts and their relationship to the biosynthesis of ergosterol

The sterols of four mutant strains of Saccharomyces cerevisiae have been isolated and characterised and the mutations have been related to the pathway for ergosterol biosynthesis. The effects of the mutations are to block, respectively, the introduction of the side chain methyl group, the introduction of the 5,6- and 22,23-double bonds, and the Δ8→Δ7 isomerisation. The following sterols previously unreported in yeast have been isolated and characterised: cholesta-5,7,24-trien-3β-ol (2; R = H), ergost-8-en-3β-ol, ergosta-8,22-dien-3β-ol (5; R = H), ergosta-5,8,22-trien-3β-ol (6; R = H), and ergosta-5,7-dien-3β-ol. Cholesta-5,7,22,24-tetraen-3β-ol, ergosta-8,22,24(28)-trien-3β-ol, and ergosta-8,14,24(28)-trien-3β-ol, which were previously unknown, have also been isolated and characterised.

Electrophilic fluorination in the synthesis of new fluoroindoles

Abstract Fluorination of trialkylstannylindoles with caesium fluoroxysulfate or Selectfluor was investigated for the synthesis of inter-alia 2- and 3-fluoroindoles. Caesium fluoroxysulfate gave good yields of these potentially useful intermediates; Selectfluor provided lower yields.