Direct Asymmetric Amination of α‑Branched Cyclic Ketones Catalyzed by a Chiral Phosphoric Acid

Here we report the direct asymmetric amination of α-substituted cyclic ketones catalyzed by a chiral phosphoric acid, yielding products with a N-containing quaternary stereocenter in high yields and excellent enantio­selectivities. Kinetic resolution of the starting ketone was also found to occur on some of the substrates under milder conditions, providing enantio­enriched α-branched ketones, another important building block in organic synthesis. The utility of this methodology was demonstrated in the short synthesis of (<i>S</i>)-ketamine, the more active enantiomer of this versatile pharmaceutical

Direct Asymmetric Amination of α‑Branched Cyclic Ketones Catalyzed by a Chiral Phosphoric Acid

Here we report the direct asymmetric amination of α-substituted cyclic ketones catalyzed by a chiral phosphoric acid, yielding products with a N-containing quaternary stereocenter in high yields and excellent enantio­selectivities. Kinetic resolution of the starting ketone was also found to occur on some of the substrates under milder conditions, providing enantio­enriched α-branched ketones, another important building block in organic synthesis. The utility of this methodology was demonstrated in the short synthesis of (<i>S</i>)-ketamine, the more active enantiomer of this versatile pharmaceutical

Total Synthesis of Landomycin A, a Potent Antitumor Angucycline Antibiotic

The first total synthesis of landomycin A, the longest and most potent antitumor angucycline antibiotic, has been achieved in 63 steps and 0.34% overall yield starting from 2,5-dihydroxybenzoic acid, 3,5-dimethylphenol, triacetyl d-glucal, and d-xylose, with a convergent linear sequence of 21 steps

Tailored Design of Hierarchically Porous UiO-66 with a Controlled Pore Structure and Metal Sites

Hierarchically porous metal–organic frameworks (MOFs) not only inherit the merits of MOFs such as high porosity, but they also possess distinct properties such as a broader pore size range and thus more rapid mass transport. Simple, controllable synthesis of hollow or mesoporous structures with tailored pore features and more metal sites is desired and remains challenging. Herein, we demonstrate a facile strategy for fabricating hollow/mesoporous UiO-66 through a designed defect density and subsequent etching process. The strategy relies on the construction of an inhomogeneous nanoarchitecture in which the addition of water in UiO-66 synthesis can facilitate the formation of linker defects by promoting the explosive nucleation of UiO-66 and acetic acid deprotonation, and the more defective core will be selectively etched by sodium hydroxide. The morphology, size, pore structure, and metal sites can be exquisitely designed by rationally adjusting the water dosage and etching conditions. Markedly, UiO-66 with larger mesopores contributes to excellent glyphosate adsorption capacity, and the hollow UiO-66 catalyst with more active metal sites exhibits superior performance in the [3 + 3] cycloaddition reaction

Asymmetric Synthesis of Hydroquinazolines Bearing C4-Tetrasubstituted Stereocenters via Kinetic Resolution of α‑Tertiary Amines

A novel protocol for asymmetric synthesis of hydroquinazolines bearing C4-tetrasubstituted stereocenters has been achieved through kinetic resolution of 2-amido α-tertiary benzylamines via chiral phosphoric acid catalyzed intramolecular dehydrative cyclizations. This method gave access to both α-tertiary benzylamines and hydroquinazolines with broad scope and high enantioselectivities. An intriguing restricted rotation of the C–N bond was observed for hydroquinazoline products bearing C4-tetrasubstituted stereocenters

Table3_Multi-Similarities Bilinear Matrix Factorization-Based Method for Predicting Human Microbe–Disease Associations.XLSX

Accumulating studies have shown that microbes are closely related to human diseases. In this paper, a novel method called MSBMFHMDA was designed to predict potential microbe–disease associations by adopting multi-similarities bilinear matrix factorization. In MSBMFHMDA, a microbe multiple similarities matrix was constructed first based on the Gaussian interaction profile kernel similarity and cosine similarity for microbes. Then, we use the Gaussian interaction profile kernel similarity, cosine similarity, and symptom similarity for diseases to compose the disease multiple similarities matrix. Finally, we integrate these two similarity matrices and the microbe-disease association matrix into our model to predict potential associations. The results indicate that our method can achieve reliable AUCs of 0.9186 and 0.9043 ± 0.0048 in the framework of leave-one-out cross validation (LOOCV) and fivefold cross validation, respectively. What is more, experimental results indicated that there are 10, 10, and 8 out of the top 10 related microbes for asthma, inflammatory bowel disease, and type 2 diabetes mellitus, respectively, which were confirmed by experiments and literatures. Therefore, our model has favorable performance in predicting potential microbe–disease associations.</p

Quality Control for Building Libraries from Electrospray Ionization Tandem Mass Spectra

Electrospray ionization (ESI) tandem mass spectrometry coupled with liquid chromatography is a routine technique for identifying and quantifying compounds in complex mixtures. The identification step can be aided by matching acquired tandem mass spectra (MS²) against reference library spectra as is routine for electron ionization (EI) spectra from gas chromatography/mass spectrometry (GC/MS). However, unlike the latter spectra, ESI MS² spectra are likely to originate from various precursor ions for a given target molecule and may be acquired at varying energies and resolutions and have characteristic noise signatures, requiring processing methods very different from EI to obtain complete and high quality reference spectra for individual analytes. This paper presents procedures developed for creating a tandem mass spectral library that addresses these factors. Library building begins by acquiring MS² spectra for all major MS¹ peaks in an infusion run, followed by assigning MS² spectra to clusters and creating a consensus spectrum for each. Intensity-based constraints for cluster membership were developed, as well as peak testing to recognize and eliminate suspect peaks and reduce noise. Consensus spectra were then examined by a human evaluator using a number of criteria, including a fraction of annotated peaks and consistency of spectra for a given ion at different energies. These methods have been developed and used to build a library from >9000 compounds, yielding 230,000 spectra

Table2_Multi-Similarities Bilinear Matrix Factorization-Based Method for Predicting Human Microbe–Disease Associations.XLSX

Accumulating studies have shown that microbes are closely related to human diseases. In this paper, a novel method called MSBMFHMDA was designed to predict potential microbe–disease associations by adopting multi-similarities bilinear matrix factorization. In MSBMFHMDA, a microbe multiple similarities matrix was constructed first based on the Gaussian interaction profile kernel similarity and cosine similarity for microbes. Then, we use the Gaussian interaction profile kernel similarity, cosine similarity, and symptom similarity for diseases to compose the disease multiple similarities matrix. Finally, we integrate these two similarity matrices and the microbe-disease association matrix into our model to predict potential associations. The results indicate that our method can achieve reliable AUCs of 0.9186 and 0.9043 ± 0.0048 in the framework of leave-one-out cross validation (LOOCV) and fivefold cross validation, respectively. What is more, experimental results indicated that there are 10, 10, and 8 out of the top 10 related microbes for asthma, inflammatory bowel disease, and type 2 diabetes mellitus, respectively, which were confirmed by experiments and literatures. Therefore, our model has favorable performance in predicting potential microbe–disease associations.</p

Enantioselective Dearomatization of Substituted Phenols via Organocatalyzed Electrophilic Amination

Highly efficient and stereoselective dearomatization of substituted phenols was achieved via chiral phosphoric acid-catalyzed electrophilic para-amination with commercially available azodicarboxylates. This protocol readily afforded a series of chiral 2,5-cyclohexadienones bearing 4-aza-quaternary stereocenters with excellent yields and enantioselectivities (≤99% yield and >99% ee). Easy scale-up of this reaction to a gram scale and diverse derivatizations of the chiral products into α-tertiary amines and α-tertiary heterocycles derivatives well demonstrated the potential of this method