Efficient enantioselective additions of terminal alkynes and aldehydes under operationally convenient conditions

[reaction: see text] The enantioselective addition reaction of terminal acetylenes and aldehydes mediated by Zn(OTf)2 and N-methyl ephedrine can be conducted with reagent grade solvent containing 84-1000 ppm H2O. The products can be isolated in high yield and useful enantioselectivities (up to 99% ee).     

A study of the synthesis of triazoles using microwave irradiation

Herein we describe the conversion of a known [3+2] cycloaddition reaction between an azide and an acetylene from a thermally promoted reaction to a microwave assisted process. Modification of conditions including concentration, temperature, solvent type and time were investigated. This methodology study led us to use high concentration and high temperatures to achieve the desired fast reaction times and high yields.     

Focused™ microwave instrumentation from CEM corporation

An overview of the instrumentation for microwave synthesis available from CEM Corp. is provided.     

Observation of novel liquid-crystalline phase above the bulk-melting temperature

In this paper, we show that a noncrystalline but ordered smectic-like phase exists above the bulk-melting temperature (T(m)) at poly(n-alkyl acrylates)-air interface. The surface ordered phase is one monolayer thick and undergoes a sharp transition from order to disorder 10 degrees C above T(m) for n=22. The presence of a surface phase that does not exist in the bulk has important implications in the design of thermally responsive adhesives.     

C3-symmetric trinuclear molybdenum cluster sulfides: configurational stability, supramolecular stereocontrol, and absolute configuration assignment

The chiral C3-symmetric [Mo3S4Cl3(dppe)3]+ cluster [dppe = 1,2-bis(diphenylphosphinoethane), P or M enantiomers] with incomplete cuboidal structure is shown to be configurationally stable at room temperature and configurationally labile at elevated temperature using enantiopure Delta- or Lambda-TRISPHAT [(tris(tetrachlorobenzenediolato)phosphate(V)] anions both as chiral NMR solvating and asymmetry-inducing reagents. It is evidenced that the enantiomers of this trinuclear cluster cation can equilibrate at higher temperature (typically 72 degrees C), and in the presence of the hexacoordinated phosphate anion, a moderate level of stereocontrol (1.2:1) can be achieved. It results in a diastereomeric enrichment of the solution in favor of the heterochiral ion pairs, e.g., M+ Delta- or P+ Lambda-. At higher temperature, a partial racemization of the TRISPHAT anion is also observed, and precipitation at room temperature of [rac-Mo3S4Cl3(dppe)3][rac-TRISPHAT] salts from the diastereomeric enriched solution improves the diastereomeric purity of the mother liquor to a 4:1 ratio. A low-energy pathway for the inverconversion between the [P-Mo3S4Cl3(dppe)3]+ and [M-Mo3S4Cl3(dppe)3]+ enantiomers has been found using combined quantum mechanics and molecular mechanics methodologies. This pathway involves two intermediates with three transition state regions, which result from the partial decoordination of the diphosphane coordinated at each metal center. Such decoordination creates a vacant position on the metal, producing a Lewis acidic site that presumably catalyzes the TRISPHAT epimerization.     

Understanding hERG inhibition with QSAR models based on a one-dimensional molecular representation

Blockage of the potassium channel encoded by the human ether-a-go-go related gene (hERG) is well understood to be the root cause of the cardio-toxicity of numerous approved and investigational drugs. As such, a cascade of in vitro and in vivo assays have been developed to filter compounds with hERG inhibitory activity. Quantitative structure activity relationship (QSAR) models are used at the very earliest part of this cascade to eliminate compounds that are likely to have this undesirable activity prior to synthesis. Here a new QSAR technique based on the one-dimensional representation is described in the context of the development of a model to predict hERG inhibition. The model is shown to perform close to the limits of the quality of the data used for model building. In order to make optimal use of the available data, a general robust mathematical scheme was developed and is described to simultaneously incorporate quantitative data, such as IC50 = 50 nM, and qualitative data, such as inactive or IC50 > 30 μM into QSAR models without discarding any experimental information.