Enantioselective synthesis of beta-hydroxy acid derivatives via a one-pot aldol reaction-dynamic kinetic resolution

[reaction: see text]. Combining dynamic kinetic resolution with an aldol reaction provides access to beta-hydroxy ester derivatives with high enantiomeric purity (up to 99% ee) in a one-pot procedure. Only simple starting materials are required in this enantioselective process, and preformation of a silyl enol ether is not necessary.     

Addition reaction of vinylic reagents, derived from alpha-chloroenones, to carbonyl compounds promoted by samarium diiodide

A new samarium diiodide-promoted addition reaction of vinylsamarium reagents, derived from (Z)-alpha-chloro-alpha,beta-unsaturated phenones 1, to both ketones (in THF) and aldehydes (in acetonitrile) led to (Z)-2-(1-hydroxyalkyl)-2,3-unsaturated ketones in good yield. These transformations took place with total or very high inversion of the stereochemistry of the C-C double bond of the starting chloroenone, producing the Z diastereoisomer. A new methodology to prepare SmI(2) in acetonitrile by sonic treatment of 1,2-diiodoethane with Sm powder is also described. A mechanism to explain this transformation is proposed.     

A simple shock‐capturing technique for high‐order discontinuous Galerkin methods

This article presents a novel shock‐capturing technique for the discontinuous Galerkin (DG) method. The technique is designed for compressible flow problems, which are usually characterized by the presence of strong shocks and discontinuities. The inherent structure of standard DG methods seems to suggest that they are especially adapted to capture shocks because of the numerical fluxes based on suitable approximate Riemann solvers, which, in practice, introduces some stabilization. However, the usual numerical fluxes are not sufficient to stabilize the solution in the presence of shocks for large high‐order elements. Here, a new basis of shape functions is introduced. It has the ability to change locally between a continuous or discontinuous interpolation depending on the smoothness of the approximated function. In the presence of shocks, the new discontinuities inside an element introduce the required stabilization because of numerical fluxes. Large high‐order elements can therefore be used and shocks captured within a single element, avoiding adaptive mesh refinement and preserving the locality and compactness of the DG scheme. Several numerical examples for transonic and supersonic flows are studied to demonstrate the applicability of the proposed approach. Copyright © 2011 John Wiley & Sons, Ltd.     

Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry

Interactions between kinases and small molecule inhibitors can be activation state dependent. A detailed understanding of inhibitor binding therefore requires characterizing interactions across multiple activation states. We have systematically explored the effects of ABL1 activation loop phosphorylation and PDGFR family autoinhibitory juxtamembrane domain docking on inhibitor binding affinity. For a diverse compound set, the affinity patterns correctly classify inhibitors as having type I or type II binding modes, and we show that juxtamembrane domain docking can have dramatic negative effects on inhibitor affinity. The results have allowed us to associate ligand-induced conformational changes observed in cocrystal structures with specific energetic costs. The approach we describe enables investigation of the complex relationship between kinase activation state and compound binding affinity and should facilitate strategic inhibitor design.     

A fractional-step method for the incompressible Navier–Stokes equations related to a predictor–multicorrector algorithm

An implicit fractional-step method for the numerical solution of the time-dependent incompressible Navier–Stokes equations in primitive variables is studied in this paper. The method, which is first-order-accurate in the time step, is shown to converge to an exact solution of the equations. By adequately splitting the viscous term, it allows the enforcement of full Dirichlet boundary conditions on the velocity in all substeps of the scheme, unlike standard projection methods. The consideration of this method was actually motivated by the study of a well-known predictor–multicorrector algorithm, when this is applied to the incompressible Navier–Stokes equations. A new derivation of the algorithm in a general setting is provided, showing in what sense it can also be understood as a fractional-step method; this justifies, in particular, why the original boundary conditions of the problem can be enforced in this algorithm. Two different finite element interpolations are considered for the space discretization, and numerical results obtained with them for standard benchmark cases are presented. © 1998 John Wiley & Sons, Ltd.