Gareth J. Pritchard

Paired electrosynthesis: micro-flow cell processes with and without added electrolyte

Abstract The thin layer flow cell geometry with working and auxiliary electrodes directly facing each other, allows electrosynthetic processes to be conducted in flow-through mode. At sufficiently small cell height, the two diffusion layers of working and auxiliary electrode overlap or become ‘coupled’. As a result electro-generated acids or bases are instantaneously neutralised, products from anode and cathode can interact, and, more importantly, bulk electrolysis is possible without intentionally added electrolyte. In this preliminary report, the operation of a micro-flow cell with coupled diffusion layers is demonstrated for the one electron oxidation of ferrocene and for the two electron–two proton reduction of tetraethyl ethylenetetracarboxylate dissolved in ethanol. In proof-of-principle bulk electrolysis experiments without intentionally added electrolyte, high yields of the product, tetraethyl ethanetetracarboxylate are obtained at a nickel working electrode. It is demonstrated that a sufficient concentration of electrolyte for bulk electrolysis is generated locally and in situ between working and auxiliary electrode.

Design and synthesis of novel monocyclic β-lactam inhibitors of prostate specific antigen

Abstract A novel series of monocyclic β-lactam analogues was designed using a homology derived model of prostate specific antigen (PSA) and by application of a multiple copy simultaneous search technique. Syntheses were conducted by assembly of the β-lactam core via a Staudinger reaction with elaboration at the 1, 3 and 4 positions to probe active site binding. Inhibition against PSA was evaluated.

Practical routes to diacetylenic ketones and their application for the preparation of alkynyl substituted pyridines, pyrimidines and pyrazoles

Alkynyl substituted pyridines, pyrimidines and pyrazoles have been synthesised by cyclocondensations of diacetylenic ketones with enamines, amidines and hydrazines, respectively.

Preparation of highly substituted tetrahydropyrans via a metal assisted dipolar cycloaddition reaction

A range of highly substituted tetrahydropyrans have been prepared by reaction of a donor-acceptor cyclobutane, where the donor is a metal-alkyne complex, with an aldehyde under Lewis acid conditions.

Synthesis of novel C-nucleosides with potential applications in combinatorial and parallel synthesis

Abstract Novel di-substituted pyrimidinyl C-nucleosides have been synthesised using a flexible synthetic methodology. This methodology conveniently allows the synthesis of alpha and beta nucleosides, both of which are of biological interest. Reactive acetylenic ketones, derived from 2-deoxyribose, can be reacted with substituted amidines to give new families of C-nucleoside natural product analogues.

Expedient synthesis of a highly substituted tropolone via a 3-oxidopyrylium (5+2) cycloaddition reaction

Abstract An expedient ten-step synthesis of a substituted tropolone is described. The synthesis involves a 3-oxidopyrylium [5+2] cycloaddition reaction with acrylonitrile as the key step, affording a highly functionalized [3.2.1]-bicycle 10 as a single regioisomer. The nitrile substituent of the reduced cycloadduct 12 permits efficient ether-bridge cleavage and tropolone 15 is obtained after a final bis-oxidation procedure. The pyranulose acetate cycloaddition precursor was derived from 3-methyl-2-furoate.

Concise syntheses of acromelic acid A and allo-acromelic acid A

Abstract Acromelic acid A 1 and allo -acromelic acid A 12 were synthesised in a biomimetic fashion. An oxidative cleavage - recyclisation strategy was used to construct the requisite C-4 pyridone from an intermediate catechol.

A BIOMIMETIC APPROACH TO THE PYRIDONE RINGS OF THE ACROMELIC ACIDS : A CONCISE SYNTHESIS OF ACROMELIC ACID A AND AN APPROACH TO ACROMELIC ACID B

Abstract The syntheses of acromelic acid A 1 , allo-acromelic acid A 19 and an approach towards acromelic acid B 2 are described. Palladium (0) catalysed cross-coupling reactions were used to generate C-4 catechol precursors and formation of the pyridone rings was investigated using a biomimetic oxidative cleavage - recyclisation strategy.

The synthesis of 4-arylsulfanyl-substituted kainoid analogues from trans-4-hydroxy-L-proline.

The potent neuroexcitatory activity of kainoid amino acids in the mammalian CNS places new analogues in high demand as tools for neuropharmacological research. A range of 4-arylsulfanyl-substituted kainoids has been synthesised in a parallel fashion via mesylate displacement by a number of aromatic and heteroaromatic thiolates upon (2S,3S,4R)-1-benzoyl-3-tert-butoxycarbonylmethyl-4-methanesulfo nyloxy pyrrolidine-2-carboxylic acid methyl ester 8, which is obtainable in eight steps from trans-4-hydroxy-L-proline 5.

Novel c-4 heteroaromatic kainoid analogues: a parallel synthesis approach

New C-4 thiazole 4, 5 and aminothiazole 6, 7 kainoid analogues were efficiently synthesised in five steps from commercially available (-)-alpha-kainic acid I and exhibited strong binding to the kainate receptors. A reactive alpha-bromoketone 10 was generated and reacted with thioamides and thioureas to form thiazole and aminothiazole heterocycles 11-14. Deprotection gave the new kainoid amino acids 4-7 in excellent yield.