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The enzymatic basis for quinine 1 biosynthesis was investigated. Transcriptomic data from the producing plant led to the discovery of three enzymes involved in the early and late steps of the pathway. A medium-chain alcohol dehydrogenase (CpDCS) and an esterase (CpDCE) yielded the biosynthetic intermediate dihydrocorynantheal 2 from strictosidine aglycone 3. Additionally, the discovery of an O-methyltransferase specific for 6'-hydroxycinchoninone 4 suggested the final step order to be cinchoninone 16/17 hydroxylation, methylation, and keto-reduction.A Tf2O/DMSO-based system for the dehydrogenative coupling of a wide range of alcohols, phenols, thiols, and thiophenols with diverse phosphorus reagents has been developed. This metal- and strong-oxidant-free strategy provides a facile approach to a great variety of organophosphinates and thiophosphates. The simple reaction system, good functional-group tolerance, and broad substrate scope enable the application of this method to the modification of natural products and the direct synthesis of bioactive molecules and flame retardants.A process for achieving photocatalyzed tri- and difluoromethylation/cyclizations for constructing a series of tri- or difluoromethylated indole[2,1-a]isoquinoline derivatives is described. This protocol utilized an inexpensive organic photoredox catalyst and provided good yields. Moreover, the combination of continuous flow and photochemistry, designed to provide researchers with a unique green process, was also shown to be key to allowing the reaction to proceed (product yield of 83% in flow vs 0% in batch).We have described a copper-catalyzed radical 1,2-carbotrifluoromethylselenolation of alkenes using the readily available alkyl halides and (Me4N)SeCF3 salt. Critical to the success is the use of a proline-based N,N,P-ligand to enhance the reducing capability of copper for easy conversion of diverse alkyl halides to the corresponding radicals via a single-electron transfer process. The reaction features a broad substrate scope, including various mono-, di-, and trisubstituted alkenes with many functional groups.An efficient enantioselective organocatalytic method for the synthesis of N-alkylated indoles with α-branched alkyl substituents from the corresponding unsaturated indolyl ketones via a Michael addition has been developed. The resulting products were obtained in high enantioselectivities and in good yields. Various nucleophiles (nitroalkanes, malononitrile, malonic esters) can be used. The substitution pattern of the indole ring had no significant impact on the reaction outcome. Both electron-withdrawing and electron-donating substituents in any position of the heteroaromatic ring were well-tolerated.Weak polyampholytes and globular proteins among them can be efficiently absorbed from solutions by polyelectrolyte brushes or microgels even if the net charge of the polyampholyte is of the same sign as that of the brush/microgel. We use a mean-field approach for calculating the free energy of insertion of a probe polyampholyte molecule into a polyelectrolyte brush/microgel. We anticipate that the insertion of the polyampholyte into similarly charged brush/microgel may be thermodynamically favorable due to the gain in the cumulative re-ionization free energy of the pH-sensitive acidic and basic residues. Importantly, we demonstrate that the polyampholyte (protein) charge sign inversion upon transfer from the bulk of the solution to the brush/microgel does not provide sufficient conditions to assure negative re-ionization free energy balance. Thus (in the absence of other driving or stopping mechanisms), charge sign inversion does not necessarily provoke spontaneous absorption of the polyampholyte into the brush/microgel.The copper-catalyzed selective cleavage of alkylsilyl peroxides and the subsequent formation of carbon-carbon or carbon-nitrogen bonds with organosilicon compounds are described. The reaction proceeds under mild conditions and exhibits a broad substrate scope with respect to both cyclic and acyclic alkylsilyl peroxides in combination with carbon and nitrogen sources. In particular, this approach enables the facile radical perfluoroalkylation using commercially available perfluoroalkyltrimethylsilanes. Our mechanistic studies suggest that the reaction should proceed via a free-radical process.A one-pot cascade transformation consisting of an electrochemically driven azidation of 2H-indazole followed by coarctate fragmentation is developed to synthesize the 2-azo-benzonitrile motif. This manganese-catalyzed transformation is external-chemical-oxidant-free and operates at ambient temperature under air. This methodology exhibits good functional group tolerance, affording a broad range of substrate scopes of up to 89% isolated yield. Diverse derivatization of the 2-azo-benzonitrile product resulted in other valuable scaffolds.BioContainers is an open-source project that aims to create, store, and distribute bioinformatics software containers and packages. IWP-4 order The BioContainers community has developed a set of guidelines to standardize software containers including the metadata, versions, licenses, and software dependencies. BioContainers supports multiple packaging and container technologies such as Conda, Docker, and Singularity. The BioContainers provide over 9000 bioinformatics tools, including more than 200 proteomics and mass spectrometry tools. Here we introduce the BioContainers Registry and Restful API to make containerized bioinformatics tools more findable, accessible, interoperable, and reusable (FAIR). The BioContainers Registry provides a fast and convenient way to find and retrieve bioinformatics tool packages and containers. By doing so, it will increase the use of bioinformatics packages and containers while promoting replicability and reproducibility in research.It is a challenging work to screen, identify, and quantify acylcarnitines in complex biological samples. A method, based on the retention time (RT) prediction and data-independent acquisition strategies, was proposed for the large-scale identification of acylcarnitines using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS). Relative cumulative eluotropic strength was introduced as a novel descriptor in building a linear prediction model, which not only solves the problem that acylcarnitines with long carbon chains cannot be well predicted in traditional models but also proves its robustness and transferability across instruments in two data sets that were acquired in distinct chromatography conditions. The accessibility of both predictive RT and MS2 spectra of suspect features effectively reduced about 30% false-positive results, and consequently, 150 and 186 acylcarnitines were identified in the rat liver and human plasma (NIST SRM 1950), respectively. This method provides a new approach in large-scale analysis of acylcarnitine in lipidomic studies and can also be extended to the analysis of other lipids.
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