Practical and efficient method for amino acid derivatives containing β-quaternary center: application toward synthesis of hepatitis C virus NS3 serine protease inhibitors

A practical and efficient route toward synthesis of amino acid derivatives containing β-quaternary center has been developed using diastereoselective Strecker reaction. The method was employed for preparation of >100 g of β-methylcyclohexyl glycine derivative, 21. Incorporation of some of the hindered amino acid derivatives at the P3 position resulted in potent HCV NS3 serine protease inhibitors.     

Hybrid Equilibrium Finite Elements for Wave Diffraction Problems

Hybrid equilibrium finite elements based on the direct approximation of the domain stress and boundary displacement fields are presented. The structure is divided into a far field, which is considered as an infinite super element, and a near field, which is in turn discretized into finite elements. The displacements in the domains of typical finite elements are obtained from the assumed domain stress field by using the dynamic equilibrium equations. The Helmholtz equation is satisfied in the domain of the infinite super element, and the domain stress fields are associated with elastic and compatible displacements. The resulting governing system is symmetric, sparse, and, if well done, positive. Numerical applications are presented to illustrate the performance of the formulation     

Experimental techniques employed for photoelastic analysis of cellular shells

The search for a shell construction superior to the usual ring-stiffened shells in strength and stability under external pressure with minimum weight has led to consideration of several other shell wall constructions.¹ The cellular-shell structure is one of the most promising designs of shells because of its ability to withstand high-pressure loading while maintaining a high degree of material efficiency. The analytical treatment of cellular shells has been undertaken only recently² and limited experimental study of these shells has been conducted. Thus, for obtaining reliable design formulas for the cellular-shell construction, these studies were undertaken. The cellular-shell construction may be visualized as two concentric thin cylinders spaced radially by a series of thin rings along their common longitudinal axis. The optimum wall thickness, rib thickness and rib spacing for a cellular shell of a given diameter and material which will result in the most efficient utilization of the material when the shell is placed under external pressure is the information required for shell design. The experimental techniques described in this paper have been employed to assist in the determination of the necessary design parameters.     

Stereoselective Silylcupration of Conjugated Alkynes in Water at Room Temperature

Micellar catalysis enables copper‐catalyzed silylcupration of a variety of electron‐deficient alkynes, thereby providing access to isomerically pure E‐ or Z‐β‐silyl‐substituted carbonyl derivatives. These reactions take place in minutes, afford high yields and stereoselectivity, and are especially tolerant of functional groups present in the substrates. The aqueous reaction medium has been successfully recycled several times, and a substrate/catalyst ratio of 10,000:1 has been documented for this methodology.     

High‐Performing Red‐Light‐Emitting Pyrotechnic Illuminants through the Use of Perchlorate‐Free Materials

The development of perchlorate‐free M662 40 mm illuminating pyrotechnic compositions is described. On the bases of cost, performance, and sensitivity, potassium periodate was determined to be most effective potassium perchlorate replacement in the compositions tested. The optimal periodate‐based composition exceeded the performance of the perchlorate‐containing control, exhibited low sensitivity values to impact, friction, and electrostatic discharge, and had high thermal onset temperatures.     

Mechanical and thermal investigation of thermoplastic nanocomposite films fabricated using micro- and nano-sized fillers from recycled cotton T-shirts

The thermal and mechanical performance of composites with nano-sized cotton fillers embedded in low-density polyethylene (LDPE) is investigated. Microfibrillated cotton was prepared by microgrinding mechanical treatment of pulverized cotton (pCot) derived from waste T-shirts, resulting in nano-sized fibrils of the cellulose that retain high crystallinity. Film composites of LDPE with pCot before and after microgrinding were fabricated through melt extrusion and the effect of filler size on mechanical, thermal and morphological properties of the composite was investigated. Compounding microfibrillated cotton with LDPE resulted in well-dispersed nanocomposites with no discoloration after 10 min of melt extrusion at 170 °C. At concentrations up to 10 % by weight, the composites showed increased modulus, increased tensile strength and a slight decrease in elongation to break. Further improvement in the dispersion and mechanical properties of the cotton-based fillers was realized by the use of LDPE powder instead of polymer pellets fed to the extruder. This research demonstrates the processing and applicability of the use of recycled cotton-based nano-sized fillers in melt-processing.     

Double Strain‐Promoted Macrocyclization for the Rapid Selection of Cell‐Active Stapled Peptides

Peptide stapling is a method for designing macrocyclic alpha‐helical inhibitors of protein–protein interactions. However, obtaining a cell‐active inhibitor can require significant optimization. We report a novel stapling technique based on a double strain‐promoted azide–alkyne reaction, and exploit its biocompatibility to accelerate the discovery of cell‐active stapled peptides. As a proof of concept, MDM2‐binding peptides were stapled in parallel, directly in cell culture medium in 96‐well plates, and simultaneously evaluated in a p53 reporter assay. This in situ stapling/screening process gave an optimal candidate that showed improved proteolytic stability and nanomolar binding to MDM2 in subsequent biophysical assays. α‐Helicity was confirmed by a crystal structure of the MDM2‐peptide complex. This work introduces in situ stapling as a versatile biocompatible technique with many other potential high‐throughput biological applications.