Toward a Structural View of hERG Activation by the Small-Molecule Activator ICA-105574.

Outward current conducted by human ----related gene type 1 (hERG1) K channels is important for action potential repolarization in the human ventricle. Rapid, voltage-dependent inactivation greatly reduces outward currents conducted by hERG1 channels and involves conformational changes in the ion selectivity filter (SF). Recently, compounds have been found that activate hERG1 channel function by modulating gating mechanisms such as reducing inactivation.

Unusual mechanisms in Claisen rearrangements: an ionic fragmentation leading to a -selective rearrangement.

A mechanistic investigation of the acid-catalysed redox-neutral oxoarylation reaction of ynamides using electrospray ionisation mass-spectrometry (ESI-MS) and quantum chemical calculations (DFT and MP2) is presented. This study reveals the diversity of pathways and products available from an otherwise deceptively simple-looking, classical transformation: fragmentation, an unusual -arylation and competing α-carbonyl cation pathways are some of the alternatives unveiled by ESI-MS and mechanistic experiments. Detailed calculations explain the observed trends and rationalise the results.

C2-Modified Sparteine Derivatives Are a New Class of Potentially Long-Acting Sodium Channel Blockers.

The lupin alkaloid sparteine is a well-known chiral diamine with a range of applications in asymmetric synthesis, as well as a blocker of voltage-gated sodium channels (VGSCs). However, there is only scarce information on the VGSC-blocking activity of sparteine derivatives where the structure of the parent alkaloid is retained. Building on the recent renewed availability of sparteine and derivatives we report herein how modification of sparteine at position 2 produces irreversible blockers of VGSCs.

Intramolecular hydrogen bonding in conformationally semi-rigid α-acylmethane derivatives: a theoretical NMR study.

Conformational mobility is a core property of organic compounds, and conformational analysis has become a pervasive tool for synthetic design. In this work, we present experimental and computational (employing Density Functional Theory) evidence for unusual intramolecular hydrogen bonding interactions in a series of α-acylmethane derivatives, as well as a discussion of the consequences thereof for their NMR spectroscopic properties.

A non-Diels-Alder approach to the cis-decalin core of branimycin.

The synthesis of the highly substituted cis-decalin core of branimycin has been accomplished. A catalytic copper mediated SN2' opening of oxabicycle 7 with Grignard reagent and ring-closing metathesis served as key transformations.

Global and local alignments in HIV/AIDS prevention trainings: a case study from Burkina Faso.

This article presents a linguistic analysis of data from an ongoing research project exploring HIV/AIDS education in West African Burkina Faso. I argue that we can identify different, sometimes even competing, discourses about the disease in prevention interactions. Thus, communication about HIV/AIDS in Burkina Faso--and probably in most of the Sub-Saharan countries--might be characterized by what I will call, with reference to Bakhtin, discursive heteroglossia.

Synthesis of the C1-C13 Fragment of Kendomycin: Atropisomerism around a C-Aryl Glycosidic Bond.

The left-hand fragment 2 of the novel antibiotic kendomycin (1) has been synthesized by an aldol addition and a Michael-type 1,4-addition of a C5 alcohol with a C9-C11 enone. Compound 2 shows an interesting atropisomerism around the C4a-C5-sp -sp bond. The atropisomers can be separated in pure forms by low-temperature high-pressure liquid chromatography.