The total synthesis of K-252c (staurosporinone) via a sequential C-H functionalisation strategy.

A synthesis of the bioactive indolocarbazole alkaloid K-252c (staurosporinone) via a sequential C-H functionalisation strategy is reported. The route exploits direct functionalisation reactions around a simple arene core and comprises of two highly-selective copper-catalysed C-H arylations, a copper-catalysed C-H amination and a palladium-catalysed C-H carbonylation, which build up the structural complexity of the natural product framework.

A counteranion triggered arylation strategy using diaryliodonium fluorides.

A mild and transition metal-free counteranion triggered arylation strategy has been developed using diaryliodonium fluorides. The fluoride counteranion within the hypervalent iodonium species displays unusual reactivity that activates a phenolic O-H bond leading to electrophilic O-arylation. A wide range of phenols and diaryliodonium salts are compatible with this transformation under remarkably mild conditions. Furthermore, we pre-empt the wider implications of this strategy by demonstrating the compatibility of the arylation tactic with latent carbon nucleophiles.

Potential novel targets for Alzheimer pharmacotherapy: I. Secretases.

The prevailing major theory of Alzheimer's disease (AD) is that insoluble amyloid beta-peptide (Abeta) found in the cerebral plaques characteristic of the disease is causative or is at least a contributing factor. According to this theory, inhibition of aberrant Abeta production should prevent or at least limit the extent of AD pathophysiology. As three 'secretase' enzymes (alpha, beta and gamma) catalyse the proteolytic cleavage of amyloid precursor protein (APP) (the precursor protein of Abeta), one or more secretases have become targets for potential novel AD pharmacotherapy. Secretase inhibitors have been designed and are in various stages of development. The clinical trials of these compounds will, if positive, result in drugs with dramatically better clinical efficacy or, if negative, will force a reassessment of the theory about the role of Abeta in AD.

Derailing the Wacker oxidation: development of a palladium-catalyzed amidation reaction.

[figure: see text] A conceptually new palladium-catalyzed amidation reaction is described for the synthesis of beta-amido ketones based on derailing the Wacker oxidation of enones. This reaction generates a new carbon-nitrogen bond via a palladium-catalyzed conjugate addition of a carbamate nucleophile to an enone. The regiocontrol, mild and neutral conditions, lack of preactivation of the nucleophile, and lack of reoxidation system for the catalyst are attractive features of this transformation.

Evidence that the availability of an allylic hydrogen governs the regioselectivity of the Wacker oxidation.

The allylic hydrogen is found to have a dramatic effect on the regioselectivity of the Wacker oxidation, leading to the postulation that an agostic hydrogen or enyl (sigma + pi) complex helps to stabilise the key intermediate.