Aerobic and anaerobic respiratory systems allow cells to transport the electrons to terminal electron acceptors. The quinone (ubiquinone or menaquinone) pool is central to the electron transport chain. In the majority of Gram-positive bacteria, vitamin K2 (menaquinone) is the sole quinone in the electron transport chain, and thus, the bacterial enzymes catalyzing the synthesis of menaquinone are potential targets for the development of novel antibacterial drugs. This manuscript reviews the role of vitamin K in bacteria and humans, and especially emphasizes on recent aspects of menaquinones in bacterial electron transport chain and on discoveries of inhibitor molecules targeting bacterial electron transport systems for new antibacterial agents.

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Protein kinases have become the second most important group of drug targets for the pharmaceutical industry next to G-protein-coupled receptors. Thus, over the past decade, a significant number of small molecules have been generated for protein kinase drug optimization programs. The vast majority of kinase inhibitors target the ATP binding site of the enzyme; however, the poor protein kinase selectivity of ATP-competitive protein kinase inhibitors (PKIs) limits their use for treating chronic diseases. In contrast, for inhibitors of bacterial signal transduction systems targeting bacterial kinase(s), there are no such selectivity requirements as long as the inhibitor does not act on any human kinases at the effective concentrations for killing bacteria in vivo. Protein phosphorylation in bacteria is performed by twocomponent signal transduction systems (2CSTSs) and eukaryotic-like serine/threonine kinases or bacterial tyrosine kinases. Recently, a large number of studies of protein kinases essential for sustaining bacterial growth and kinases required for virulence have been reported. Thus, bacterial protein kinases offer considerable potential as new drug targets. To identify bacterial PKIs, large chemical libraries of ATPcompetitive inhibitors developed for eukaryotic protein kinases are an invaluable asset. This manuscript reviews progress on the development of prokaryotic protein kinase inhibitors. Drug Dev Res 71:168-187, 2010.

A simple and novel synthesis of (+)-monocerin was achieved in 15 steps and 15.5% overall yield from 3-buten-1-ol employing hydrolytic kinetic resolution, Julia olefination, intramolecular tandem Sharpless asymmetric dihydroxylation-SN2 cyclization and a novel copper mediated tandem cyanation-cyclization as the key steps.

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