Zhicai Shang

The concise and highly convergent synthesis of the isodityrosine unit of seongsanamide A–D and its derivatives bearing a diaryl ether moiety is described. In this work, the synthetic strategy features palladium-catalyzed C(sp³)–H functionalization and a Cu/ligand-catalyzed coupling reaction. We report a practical protocol for the palladium-catalyzed mono-arylation of β-methyl C(sp³)–H of an alanine derivative bearing a 2-thiomethylaniline auxiliary. The reaction is compatible with a variety of functional groups, providing practical access to numerous β-aryl-α-amino acids; these acids can be converted into various tyrosine and dihydroxyphenylalanine (DOPA) derivatives. Then, a CuI/N,N-dimethylglycine-catalyzed arylation of the already synthesized DOPA derivatives with aryl iodides is described for the synthesis of isodityrosine derivatives.

Natural products are a major source of biological molecules. The 3‐methylfuran scaffold is found in a variety of plant secondary metabolite chemical elicitors that confer host‐plant resistance against insect pests. Herein, the diversity‐oriented synthesis of a natural‐product‐like library is reported, in which the 3‐methylfuran core is fused in an angular attachment to six common natural product scaffolds—coumarin, chalcone, flavone, flavonol, isoflavone and isoquinolinone. The structural diversity of this library is assessed computationally using cheminformatic analysis. Phenotypic high‐throughput screening of β‐glucuronidase activity uncovers several hits. Further in vivo screening confirms that these hits can induce resistance in rice to nymphs of the brown planthopper Nilaparvata lugens. This work validates the combination of diversity‐oriented synthesis and high‐throughput screening of β‐glucuronidase activity as a strategy for discovering new chemical elicitors.

To provide essential information for peptide inhibitor design, the interactions of Eps15 homology domain of Eps15 homology domain-containing protein 1 (EHD

Protein-peptide interactions are prevalent and play essential roles in many living activities. Peptides recognize their protein partners by direct nonbonded interactions and indirect adjustment of conformations. Although processes of protein-peptide recognition have been comprehensively studied in both sequences and structures recently, flexibility of peptides and the configuration entropy penalty in recognition did not get enough attention. In this study, 20 protein-peptide complexes and their corresponding unbound peptides were investigated by molecular dynamics simulations. Energy analysis revealed that configurational entropy penalty introduced by restriction of the degrees of freedom of peptides in indirect readout process of protein-peptide recognition is significant. Configurational entropy penalty has become the main content of the indirect readout energy in protein-peptide recognition instead of deformation energy which is the main source of the indirect readout energy in classical biomolecular recognition phenomena, such as protein–DNA binding. These results provide us a better understanding of protein-peptide recognition and give us some implications in peptide ligand design.

The copper-catalyzed C–N cross-coupling of poorly nucleophilic acyclic secondary amides with sterically hindered substituted 2-halobenzoates has been demonstrated with 1,4-dimethyl-3,4-dihydro-1H-benzo[e][1,4]diazepin-5(2H)-one (DMBDO) as ligands for the first time. The protocol is effective for the synthesis of hindered tertiary amides. We also found that the alkoxycarbonyl (CO₂R) group has a strong ortho-substituent effect on a Goldberg-type C–N coupling reaction.

A general and efficient Cu(II)‐catalyzed cross‐coupling method is reported for the preparation of acyclic tertiary amides. Generally moderate to excellent yields and functional group tolerance were obtained with secondary acyclic amides and aryl halides as substrates in toluene.

A systematic study of integrating statistical modeling and experimental analysis to investigate the cloud point (CP) and environmental risk of 82 structurally diverse nonionic surfactants is performed. During this procedure, the structural profiles of the studied compounds are characterized using hydrophilic domain and the whole molecular. Hundreds of descriptors, including constitutional, topological, geometrical, and electrostatic were calculated by the CODESSA program, and the resulting variables of the characterization selected by heuristic method are then modeled by the Gaussian process (GP). A variety of regression techniques, including MLR, PLS, SVM, and LSSVM are performed to a comprehensive comparison with GP on the basis of statistical analysis and experimental properties, in conjunction with the sophisticated variable selection methods, that is, empirical heuristic strategy. Among all the built models, the most predictable one is constructed based on the GP modeling combination of heuristic variable selection related to hydrophilic domain, with its predictive coefficient of determination ( ) and root-mean-square error of prediction (RMSP) on external independent test set of 0.962 and 5.200, respectively. The statistic model shows that the CP phenomenon is a comprehensive interaction of relative molecular weight, moments of inertia A, and topological structure account for hydrophilic part.

L-lysine was applied to the synthesis of 3-substituted coumarins through the condensation of various salicylaldehyde with reactive methylene compounds in water. In this work, waste minimization, catalyst recovery, simple operation and easier product work-up were achieved.

The L-proline-catalyzed oxidation of aliphatic primary alcohols with N-bromosuccimide (NBS) in water at room temperature to afford the corresponding dimeric esters in good to excellent yields was described. This pathway of dimeric esterification was proved to be very simple and environmentally friendly.

A systematic theoretical investigation on the interaction energies of halogen-ionic bridges formed between halide ions and the polar H atoms bonded to N of protein moieties has been carried out by employing a variety of density functional methods. In this procedure, full geometry optimizations are performed at the Møller-Plesset second-order perturbation (MP2) level of theory in conjunction with the Dunning’s augmented correlation-consistent basis set, aug-cc-pVDZ. Subsequently, two distinct basis sets, i.e. 6-311++G(df,pd) and aug-cc-pVTZ, are employed in the following single-point calculations so as to check the stability of the results obtained at the different levels of DFT. The performance of DFT methods has been evaluated by comparing the results with those obtained from the rigorous MP2 theory. It is shown that the B98, B97-1, and M05 give the lowest root-mean-square error (RMSE) for predicting fluoride-binding energies, M05-2X, MPW1B95, and MPW1PW91 have the best performance in reproducing chloride-binding energies, B97-1, PBEKCIS, and PBE1KCIS present the optimal result for bromide-binding energies, while B97-1, MPW1PW91, and TPSS perform most well on iodide-binding energies. The popular B3LYP functional seems to be quite modest for studying halide-protein moiety interactions. In addition, the PBE1KCIS functional provide accuracies close to the computationally expensive MP2 method for the calculation of interaction energies of all halide-binding systems.