RASS‐Enabled S/P−C and S−N Bond Formation for DEL Synthesis

DNA encoded libraries (DEL) have shown promise as a valuable technology for democratizing the hit discovery process. Although DEL provides relatively inexpensive access to libraries of unprecedented size, their production has been hampered by the idiosyncratic needs of the encoding DNA tag relegating DEL compatible chemistry to dilute aqueous environments. Recently reversible adsorption to solid support (RASS) has been demonstrated as a promising method to expand DEL reactivity using standard organic synthesis protocols. Here we demonstrate a suite of on‐DNA chemistries to incorporate medicinally relevant and C?S, C?P and N?S linkages into DELs, which are underrepresented in the canonical methods.     

gem-Diol-Type Intermediate in the Activation of a Ketone on Sn-β Zeolite as Studied by Solid-State NMR Spectroscopy

Lewis acid zeolites have found increasing application in the field of biomass conversion, in which the selective transformation of carbonyl-containing molecules is of particular importance due to their relevance in organic synthesis. Mechanistic insight into the activation of carbonyl groups on Lewis acid sites is challenging and critical for the understanding of the catalytic process, which requires the identification of reaction intermediates. Here we report the observation of a stable surface gem-diol-type species in the activation of acetone on Sn-β zeolite. ¹³C, ¹¹⁹Sn, and ¹³C–¹¹⁹Sn double-resonance NMR spectroscopic studies demonstrate that only the open Sn site ((SiO)₃Sn-OH) on Sn-β is responsible for the formation of the surface species. ¹³C MAS NMR experiments together with density functional theory calculations suggest that the gem-diol-type species exhibits high reactivity and can serve as an active intermediate in the Meerwein—Ponndorf–Verley–Oppenauer (MPVO) reaction of acetone with cyclohexanol. The gem-diol-type species offers an energy-preferable pathway for the direct carbon-to-carbon hydrogen transfer between ketone and alcohol. The results provide new insights into the transformation of carbonyl-containing molecules catalyzed by Lewis acid zeolites.     

Nucleophilic Opening of N-Carboalkoxy-2,3-anhydro-1-deoxymannojirimycin. A Useful Method for the Syntheses of 2-, 3- and 2,3-Disubstituted 1-Deoxynojirimycin Analogs

Abstract

A useful methodology for the synthesis of a number of 2-, 3- and 2,3-disubstituted deoxynojirimycin analogs is reported. It has been found that the epoxides in stereoselectively synthesized N-carboalkoxy-2,3-anhydro-1-deoxymannojirimycins (4 and 5) react with N-, S- and F- nucleophiles to give a mixture of gluco and altro products. The 3-azido altro compound (12b) yields the desired gluco derivative (40) by oxidation, in situ epimerization at C-3, followed by stereoselective reduction of the carbonyl group. The azido intermediate (12a) affords the 2,3-diazido gluco compound (51) by double inversion at C-3. Attempts have been made to understand the factors contributing to the opening of epoxides (4, 5 and 9) by different nucleophiles.     

A Molecular Toolkit for the Functionalization of Titanium‐Based Biomaterials That Selectively Control Integrin‐Mediated Cell Adhesion

We present a click chemistry‐based molecular toolkit for the biofunctionalization of materials to selectively control integrin‐mediated cell adhesion. To this end, α5β1‐selective RGD peptidomimetics were covalently immobilized on Ti‐based materials, and the capacity to promote the selective binding of α5β1 was evaluated using a solid‐phase integrin binding assay. This functionalization strategy yielded surfaces with a nine‐fold increased affinity for α5β1, in comparison to control samples, and total selectivity against the binding of the closely related integrin αvβ3. Moreover, our methodology allowed the screening of several phosphonic acid containing anchoring units to find the best spacer–anchor moiety required for establishing an efficient binding to titanium and to promote selective integrin binding. The integrin subtype specificity of these biofunctionalized surfaces was further examined in vitro by inducing selective adhesion of genetically modified fibroblasts, which express exclusively the α5β1 integrin. The versatility of our molecular toolkit was proven by shifting the cellular specificity of the materials from α5β1‐ to αvβ3‐expressing fibroblasts by using an αvβ3‐selective peptidomimetic as coating molecule. The results shown here represent the first functionalization of Ti‐based materials with α5β1‐ or αvβ3‐selective peptidomimetics that allow an unprecedented control to discriminate between α5β1‐ and αvβ3‐mediated adhesions. The role of these two integrins in different biological events is still a matter of debate and is frequently discussed in literature. Thus, such bioactive titanium surfaces will be of great relevance for the study of integrin‐mediated cell adhesion and the development of new biomaterials targeting specific cell types.     

Synthesis,Characterisation and In Vitro Anticancer Activity of Hexanuclear Thiolato‐Bridged Arene Ruthenium Metalla‐Prisms

Hexanuclear thiolato‐bridged arene ruthenium metalla‐prisms of the general formula [(p‐cymene)₆Ru₆(SR)₆(tpt)₂]⁶⁺ (R=CH₂Ph, CH₂C₆H₄‐p‐tBu, CH₂CH₂Ph; tpt=2,4,6‐tris(4‐pyridyl)‐1,3,5‐triazine), obtained from the dinuclear precursors [(p‐cymene)₂Ru₂(SR)₂Cl₂], AgCF₃SO₃ and tpt, have been isolated and fully characterised as triflate salts. The metalla‐prisms are highly cytotoxic against human ovarian cancer cells, especially towards the cisplatin‐resistant cell line A2780cisR (IC₅₀ <0.25 μM ).     

Index Calculation Attacks on RSA Signature and Encryption

At Crypto ’85, Desmedt and Odlyzko described a chosen-ciphertext attack against plain RSA encryption. The technique can also be applied to RSA signatures and enables an existential forgery under a chosen-message attack. The potential of this attack remained untapped until a twitch in the technique made it effective against two very popular RSA signature standards, namely iso/iec 9796-1 and iso/iec 9796-2. Following these attacks, iso/iec 9796-1 was withdrawn and ISO/IEC 9796-2 amended. In this paper, we explain in detail Desmedt and Odlyzko’s attack as well as its application to the cryptanalysis of iso/iec 9796-2. AMS Classification: 11T71, 14G50, 94A60     

Kramers Equation and Supersymmetry

Hamilton’s equations with noise and friction possess a hidden supersymmetry, valid for time-independent as well as periodically time-dependent systems. It is used to derive topological properties of critical points and periodic trajectories in an elementary way. From a more practical point of view, the formalism provides new tools to study the reaction paths in systems with separated time scales. A ‘reduced current’ which contains the relevant part of the phase space probability current is introduced, together with strategies for its computation.     

Preparation of a xanthate‐terminated dextran by click chemistry: Application to the synthesis of polysaccharide‐coated nanoparticles via surfactant‐free ab initio emulsion polymerization of vinyl acetate

Stable monodisperse poly(vinyl acetate) (PVAc) submicronic latex particles were synthesized by ab initio batch emulsion polymerization using a dextran derivative from renewable resource as an efficient steric stabilizer. The dextranend‐functionalized by a xanthate moiety was synthesized by Huisgen's 1,3‐dipolar cycloaddition (click chemistry). It was applied as a macromolecular RAFT (reversible addition fragmentation chain transfer) agent in surfactant‐free emulsion polymerization of vinyl acetate to form in situ an amphiphilic block copolymer able to efficiently stabilize the latex particles. The method afforded the preparation of high solids content (27%) latices coated by dextran. Both the kinetic study and the molar mass analyses confirmed the involvement of the dithiocarbonate group in the emulsion polymerization process. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2845–2857, 2008