An efficient synthesis of varenicline

Synthesis of varenicline the antismoking drug has been achieved in six steps with 10% overall yield. A Diels-Alder reaction, oxidative cleavage of an olefin and reductive amination remain as key steps in the synthesis     

A constrained optimization approach to finite element mesh smoothing

The quality of a finite element solution has been shown to be affected by the quality of the underlying mesh. A poor mesh may lead to unstable and/or inaccurate finite element approximations. Mesh quality is often characterized by the “smoothness” or “shape” of the elements (triangles in 2-D or tetrahedra in 3-D). Most automatic mesh generators produce an initial mesh where the aspect ratio of the elements are unacceptably high. In this paper, a new approach to produce acceptable quality meshes from a topologically valid initial mesh is presented. Given an initial mesh (nodal coordinates and element connectivity), a “smooth” final mesh is obtained by solving a constrained optimization problem. The variables for the iterative optimization procedure are the nodal coordinates (excluding, the boundary nodes) of the finite element mesh, and appropriate bounds are imposed on these to prevent an unacceptable finite element mesh. Examples are given of the application of the above method for 2- and 3-D meshes generated using automatic mesh generators. Results indicate that the new method not only yields better quality elements when compared with the traditional Laplacian smoothing, but also guarantees a valid mesh unlike the Laplacian method.     

System optimal and user equilibrium time-dependent traffic assignment in congested networks

This paper formulates two dynamic network traffic assignment models in which O-D desires for the planning horizon are assumed known a priori: the system optimal (SO) and the user equilibrium (UE) time-dependent traffic assignment formulations. Solution algorithms developed and implemented for these models incorporate a traffic simulation model within an overall iterative search framework. Experiments conducted on a test network provide the basis for a comparative analysis of system performance under the SO and UE models.     

Sensitive and Multiplexed On‐chip microRNA Profiling in Oil‐Isolated Hydrogel Chambers

Although microRNAs (miRNAs) have been shown to be excellent indicators of disease state, current profiling platforms are insufficient for clinical translation. Here, we demonstrate a versatile hydrogel‐based microfluidic approach and novel amplification scheme for entirely on‐chip, sensitive, and highly specific miRNA detection without the risk of sequence bias. A simulation‐driven approach is used to engineer the hydrogel geometry and the gel‐reaction environment is chemically optimized for robust detection performance. The assay provides 22.6 fM sensitivity over a three log range, demonstrates multiplexing across at least four targets, and requires just 10.3 ng of total RNA input in a 2 hour and 15 minutes assay.     

Facile synthesis of unusual glycosyl carbamates and amino acid glycosides from propargyl 1,2-orthoesters as glycosyl donors

Propargyl 1,2-O-orthoesters are exploited for the synthesis of 1,2-trans O-glycosides of protected amino acids. N-Fmoc- and N-Cbz protected serine/threonine - benzyl/methyl esters reacted well with glucosyl-, galactosyl-, mannosyl- and lactosyl- derived propargyl 1,2-orthoesters affording respective 1,2-trans glycosides in good yields under AuBr(3)/4 ? MS Powder/CH(2)Cl(2)/rt. t-Boc serine derivative gave serine 1,2-orthoester and glycosyl carbamate. Optimized conditions enabled preparation of new glycosyl carbamates from N-Boc protected amines in a single step using gold catalysts and propargyl 1,2-orthoesters in excellent yields.     

Stereoselective Total Synthesis of Rugulactone

The stereoselective synthesis of the naturally occurring dihydropyranone rugulactone has been accomplished starting from 3‐phenylpropan‐1‐ol employing Maruoka allylation and ring‐closing metathesis as the key steps.