Harnessing the ambiphilicity of silyl nitronates in a catalytic asymmetric approach to aliphatic β³-amino acids

Nitronate anions, formally generated by α-deprotonating the corresponding nitroalkanes, are highly nucleophilic and versatile intermediates in many carbon–carbon bond-forming reactions. In contrast, the corresponding silyl nitronates are ambiphilic and react, at the same carbon atom, with both electrophiles and nucleophiles. However, while their nucleophilicity has been well exploited in catalytic enantioselective reactions with imines and aldehydes, utilizing the electrophilicity of silyl nitronates in asymmetric synthesis has remained elusive. Here we report the facile, efficient and general reactivity of readily available silyl nitronates with silyl ketene acetals, catalysed by highly Lewis-acidic and confined silylium imidodiphosphorimidate catalysts. The products of this reaction, so-called nitroso acetals, are obtained in excellent enantioselectivity and can be easily converted into N-Boc-β3-amino acid esters in a single step

Direct and Catalytic C-Glycosylation of Arenes: Expeditious Synthesis of the Remdesivir Nucleoside

Since early 2020, scientists have strived to find an effective solution to fight SARS-CoV-2, especially by developing reliable vaccines that inhibit the spread of the disease and repurposing drugs for combatting its effects on the human body. The antiviral prodrug Remdesivir is still the most widely used therapeutic during the early stage of the infection. However, the current synthetic routes rely on the use of protecting groups, air-sensitive reagents, and cryogenic conditions, impeding the cost-efficient supply to patients. We therefore focused on the development of a straightforward, direct addition of (hetero)arenes to unprotected sugars. Here we report a silylium-catalyzed and completely stereoselective C -glycosylation that initially yields the open-chain polyols, which can be selectively cyclized to provide either the kinetic α-furanose or the thermodynamically favored β-anomer. The method significantly expedites the synthesis of Remdesivir precursor GS-441524 after subsequent Mn-catalyzed C–H oxidation and deoxycyanation

Conflict experience and resolution underlying obedience to authority

Definitions of obedience require the experience of conflict in response to an authority’s demands. Nevertheless, we know little about this conflict and its resolution. Two experiments tested the suitability of the ‘object-destruction paradigm’ for the study of conflict in obedience. An experimenter instructed participants to shred bugs (among other objects) in a manipulated coffee grinder. In contrast to the demand condition, participants in the control condition were reminded of their free choice. Both received several prods if they defied the experimenter. Results show that participants were more willing to kill bugs in the demand condition. Self-reported negative affect was increased after instructions to destroy bugs relative to other objects (Experiments 1 and 2). In Experiment 2, compliant participants additionally showed an increase in tonic skin conductance and, crucially, self-reported more agency and responsibility after alleged bug-destruction. These findings elucidate the conflict experience and resolution underlying obedience. Implications for prominent explanations (agentic shift, engaged followership) are discussed

Conflict experience and resolution underlying obedience to authority

Definitions of obedience require the experience of conflict in response to an authority’s demands. Nevertheless, we know little about this conflict and its resolution. Two experiments tested the suitability of the ‘object-destruction paradigm’ for the study of conflict in obedience. An experimenter instructed participants to shred bugs (among other objects) in a manipulated coffee grinder. In contrast to the demand condition, participants in the control condition were reminded of their free choice. Both received several prods if they defied the experimenter. Results show that participants were more willing to kill bugs in the demand condition. Self-reported negative affect was increased after instructions to destroy bugs relative to other objects (Experiments 1 and 2). In Experiment 2, compliant participants additionally showed an increase in tonic skin conductance and, crucially, self-reported more agency and responsibility after alleged bug-destruction. These findings elucidate the conflict experience and resolution underlying obedience. Implications for prominent explanations (agentic shift, engaged followership) are discussed

Optical Solitary Waves in the Higher Order Nonlinear Schrodinger Equation

We study solitary wave solutions of the higher order nonlinear Schrodinger equation for the propagation of short light pulses in an optical fiber. Using a scaling transformation we reduce the equation to a two-parameter canonical form. Solitary wave (1-soliton) solutions exist provided easily met inequality constraints on the parameters in the equation are satisfied. Conditions for the existence of N-soliton solutions (N>1) are determined; when these conditions are met the equation becomes the modified KdV equation. A proper subset of these conditions meet the Painleve plausibility conditions for integrability.Comment: REVTeX, 4 pages, no figures. To appear in Phys. Rev. Let

Heat-Shock Protein 90 Controls the Expression of Cell-Cycle Genes by Stabilizing Metazoan-Specific Host-Cell Factor HCFC1

Molecular chaperones such as heat-shock proteins (HSPs) help in protein folding. Their function in the cytosol has been well studied. Notably, chaperones are also present in the nucleus, a compartment where proteins enter after completing de novo folding in the cytosol, and this raises an important question about chaperone function in the nucleus. We performed a systematic analysis of the nuclear pool of heat-shock protein 90. Three orthogonal and independent analyses led us to the core functional interactome of HSP90. Computational and biochemical analyses identify host cell factor C1 (HCFC1) as a transcriptional regulator that depends on HSP90 for its stability. HSP90 was required to maintain the expression of HCFC1-targeted cell-cycle genes. The regulatory nexus between HSP90 and the HCFC1 module identified in this study sheds light on the relevance of chaperones in the transcription of cell-cycle genes. Our study also suggests a therapeutic avenue of combining chaperone and transcription inhibitors for cancer treatment

Experimental feasibility of measuring the gravitational redshift of light using dispersion in optical fibers

This paper describes a new class of experiments that use dispersion in optical fibers to convert the gravitational frequency shift of light into a measurable phase shift or time delay. Two conceptual models are explored. In the first model, long counter-propagating pulses are used in a vertical fiber optic Sagnac interferometer. The second model uses optical solitons in vertically separated fiber optic storage rings. We discuss the feasibility of using such an instrument to make a high precision measurement of the gravitational frequency shift of light.Comment: 11 pages, 12 figure

Leading Order Temporal Asymptotics of the Modified Non-Linear Schrodinger Equation: Solitonless Sector

Using the matrix Riemann-Hilbert factorisation approach for non-linear evolution equations (NLEEs) integrable in the sense of the inverse scattering method, we obtain, in the solitonless sector, the leading-order asymptotics as $t$ tends to plus and minus infinity of the solution to the Cauchy initial-value problem for the modified non-linear Schrodinger equation: also obtained are analogous results for two gauge-equivalent NLEEs; in particular, the derivative non-linear Schrodinger equation.Comment: 29 pages, 5 figures, LaTeX, revised version of the original submission, to be published in Inverse Problem

Diphenyl Urea Derivatives as Inhibitors of Transketolase: A Structure-Based Virtual Screening

Transketolase is an enzyme involved in a critical step of the non-oxidative branch of the pentose phosphate pathway whose inhibition could lead to new anticancer drugs. Here, we report new human transketolase inhibitors, based on the phenyl urea scaffold, found by applying structure-based virtual screening. These inhibitors are designed to cover a hot spot in the dimerization interface of the homodimer of the enzyme, providing for the first time compounds with a suggested novel binding mode not based on mimicking the thiamine pyrophosphate cofactor

Stokes solitons in optical microcavities

Solitons are wave packets that resist dispersion through a self-induced potential well. They are studied in many fields, but are especially well known in optics on account of the relative ease of their formation and control in optical fibre waveguides. Besides their many interesting properties, solitons are important to optical continuum generation, in mode-locked lasers, and have been considered as a natural way to convey data over great distances. Recently, solitons have been realized in microcavities, thereby bringing the power of microfabrication methods to future applications. This work reports a soliton not previously observed in optical systems, the Stokes soliton. The Stokes soliton forms and regenerates by optimizing its Raman interaction in space and time within an optical potential well shared with another soliton. The Stokes and the initial soliton belong to distinct transverse mode families and benefit from a form of soliton trapping that is new to microcavities and soliton lasers in general. The discovery of a new optical soliton can impact work in other areas of photonics, including nonlinear optics and spectroscopy