Synthesis of chimeric oligonucleotides containing phosphodiester, phosphorothioate, and phosphoramidate linkages

[reaction: see text] H-Phosphonate monomers of 2'-O-(2-methoxyethyl) ribonucleosides have been synthesized. Oxidation of oligonucleotide H-phosphonates has been optimized to allow the synthesis of oligonucleotides containing either 2'-deoxy or 2'-O-(2-methoxyethyl) ribonucleoside residues combined with three different phosphate modifications in the backbone, i.e., phosphodiester (PO), phosphorothioate (PS), and phosphoramidate (PN). Phosphodiester linkages were introduced by oxidation with a cocktail of 0.1 M Et(3)N in CCl(4)/Pyr/H(2)O (5:9:1) without affecting phosphorothioate or phosphoramidate linkages. For the synthesis of phosphoramidate-modified oligonucleotides, N(4)-acetyl deoxycytidine-3'-H-phosphonate monomers were used to avoid transamination during the oxidation step.     

Nucleophilic substitution approach towards 1,3-dimethylbarbituric acid derivatives—new synthetic routes and crystal structures

We describe simple, convenient and high-yielding nucleophilic substitution reactions to synthesize new derivatives of 1,3-dimethylbarbituric acid (1a). Based on its active C5 position, condensing 1a with sulfuryl chloride gives the corresponding 5,5-dichloro-1,3-dimethylbarbituric acid (13). The latter was reacted with silver nitrite and potassium cyanide to afford 5-chloro-5-nitro-1,3-dimethylbarbituric acid (14) and 5-cyano-1,3-dimethylbarbiturate (17), respectively. Furthermore, by employing the nucleophilic character of 2,3-dihydro-1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene (8) the obtained compounds 13 and 14 have been converted to 2-chloro-1,3-diisopropyl-4,5-dimethyl-1H-imidazol-3-ium-1,3-dimethyl-5-nitro-1,3-dimethylbarbiturate (18) and 1,3-dimethylbarbituric acid trimer (21), respectively. X-ray structures for compounds 13, 14, 17, 18 and 21 were determined.     

Single‐Layered Ultrasmall Nanoplates of MoS2 Embedded in Carbon Nanofibers with Excellent Electrochemical Performance for Lithium and Sodium Storage

The preparation and electrochemical storage behavior of MoS₂ nanodots—more precisely single‐layered ultrasmall nanoplates—embedded in carbon nanowires has been studied. The preparation is achieved by an electrospinning process that can be easily scaled up. The rate performance and cycling stability of both lithium and sodium storage were found to be outstanding. The storage behavior is, moreover, highly exciting from a fundamental point of view, as the differences between the usual storage modes—insertion, conversion, interfacial storage—are beneficially blurred. The restriction to ultrasmall reaction domains allows for an almost diffusion‐less and nucleation‐free “conversion”, thereby resulting in a high capacity and a remarkable cycling performance.     

Selector‐Induced Dynamic Deracemization of a Selectand‐Modified Tropos BIPHEPO‐Ligand: Application in the Organocatalyzed Asymmetric Double‐Aldol‐Reaction

Stereolabile interconverting catalysts open up the possibility of directing enantioselectivity in asymmetric synthesis by formation of diastereomeric complexes with chiral auxiliaries and deracemization. However, the stoichiometrically used auxilliaries can significantly limit the potential applications of such systems. We synthesized a new BIPHEPO tropos ligand containing achiral selectands in the backbone, which forms transient diastereomeric associates with amylose‐tris‐3,5‐dimethylphenyl carbamate as a selector and thus deracemizes. The enantiomerically enriched BIPHEPO obtained was successfully used in the organocatalytic asymmetric double aldol addition of substituted methyl ketones to form benzaldehyde. This strategy combines an on‐column deracemization with the high stereoinduction of chiral biarylphosphineoxides and opens up new possibilities in the field of self‐amplified asymmetric syntheses.     

Enantiomeric separation of 1,3‐dimethylamylamine by capillary electrophoresis with indirect UV detection using a dual‐selector system

The CE method employing an indirect UV detection for the enantioseparation of 1,3‐dimethylamylamine (DMAA), widely used in various preworkout and dietary supplements labeled as a constituent of geranium extract has been developed. The dual‐selector system consisting of negatively charged sulfated α‐CD (1.1% w/v) and sulfated β‐CD (0.2% w/v) in 5 mM phosphate/Tris buffer (pH 3.0) containing the addition of 10 mM benzyltriethylammonium chloride (BTEAC) as the chromophoric additive was used for the enantiomeric separation of DMAA stereoisomers with the LODs in the range of 7.82–9.24 μg/mL. The method was partly validated and applied for the determination of the stereoisomeric composition of DMAA in commercial dietary supplements to verify the potential natural origin of DMAA.     

Synthesis and Characterization of 5‐Cyanotetrazolide‐Based Ionic Liquids

New salts based on imidazolium, pyrrolidinium, phosphonium, guanidinium, and ammonium cations together with the 5‐cyanotetrazolide anion [C₂N₅]^? are reported. Depending on the nature of cation–anion interactions, characterized by XRD, the ionic liquids (ILs) have a low viscosity and are liquid at room temperature or have higher melting temperatures. Thermogravimetric analysis, cyclic voltammetry, viscosimetry, and impedance spectroscopy display a thermal stability up to 230 °C, an electrochemical window of 4.5 V, a viscosity of 25 mPa s at 20 °C, and an ionic conductivity of 5.4 mS cm^?1 at 20 °C for the IL 1‐butyl‐1‐methylpyrrolidinium 5‐cyanotetrazolide [BMPyr][C₂N₅]. On the basis of these results, the synthesized compounds are promising electrolytes for lithium‐ion batteries.     

Biology‐Oriented Synthesis of a Withanolide‐Inspired Compound Collection Reveals Novel Modulators of Hedgehog Signaling

Biology‐oriented synthesis employs the structural information encoded in complex natural products to guide the synthesis of compound collections enriched in bioactivity. The trans‐hydrindane dehydro‐δ‐lactone motif defines the characteristic scaffold of the steroid‐like withanolides, a plant‐derived natural product class with a diverse pattern of bioactivity. A withanolide‐inspired compound collection was synthesized by making use of three key intermediates that contain this characteristic framework derivatized with different reactive functional groups. Biological evaluation of the compound collection in cell‐based assays that monitored biological signal‐transduction processes revealed a novel class of Hedgehog signaling inhibitors that target the protein Smoothened.     

Investigation of monovalent and bivalent enantioselective molecular recognition by electrospray ionization-mass spectrometry and tandem mass spectrometry

In this work is described the investigation of bivalent versus monovalent enantioselective molecular recognition in the context of enantioselective separations. Electrospray ionization-mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS) are used for evaluating enantioselective systems through the measurement of (1) relative solution-phase binding constants via titration and (2) relative gas-phase binding via collision threshold dissociation. In HPLC, a cinchonane-type chiral stationary phase (CSP) based on tert.-butylcarbamoylquinine provides vastly increased retention and enantioselectivity for separation of bivalent versus monovalent alkoxy-benzoyl-N-blocked leucine enantiomers. The bivalent enantiomers are able to span and simultaneously interact with multiple interaction sites on the CSP surface, leading to enhanced separation. ESI-MS titration measurements also show an increased avidity for binding between bivalent selector and bivalent selectand, compared with the monovalent system. However, enhanced enantioselectivities measured in HPLC for the bivalent system cannot be reproduced by MS due to inherent mechanistic differences. Assumed discrepancies in relative response factors also give rise to systematic errors which are discussed. The results of MS/MS gas-phase experiments show that enantioselectivity is essentially lost in the absence of solvation, but that dissociation thresholds can provide a measure of relative dissociation energy in the bivalent interaction system compared to the monovalent counterpart. Such measurements may prove useful and efficient in better understanding multivalent interactions, in line with current theoretical considerations of effective concentrations and ion trap effects. This is the first application of mass spectrometric methods for assessing increased avidity of binding in multivalent enantioselective molecular recognition.