A practical and efficient stereoselective synthesis of arylglycine derivatives was realized via palladium-catalyzed α-arylation of a chiral nickel(II) glycinate complex with aryl bromides. The structurally diverse arylglycine products were obtained in excellent isolated yields and with good diastereoselectivity. A simple acidic hydrolysis furnished optically pure arylglycines in high yield, and the chiral ligand (S)-BPB could be efficiently recovered and reused.

Proprotein convertase subtilisin kexin 9 (PCSK9) has been identified as a reliable therapeutic target for hypercholesterolemia and coronary artery heart diseases since the monoclonal antibodies of PCSK9 have launched. Disrupting the protein–protein interaction (PPI) between PCSK9 and the low-density lipoprotein receptor (LDLR) has been considered as a promising approach for developing PCSK9 inhibitors. However, PPIs have been traditionally considered difficult to target by small molecules since the PPI surface is usually large, flat, featureless, and without a “pocket” or “groove” for ligand binding. The PCSK9-LDLR PPI interface is such a typical case. In this study, a potential binding pocket was generated on the PCSK9-LDLR PPI surface of PCSK9 through induced-fit docking. On the basis of this induced binding pocket, virtual screening, molecular dynamics (MD) simulation, and biological evaluations have been applied for the identification of novel small molecule inhibitors of PCSK9-LDLR PPI. Among the selected compounds, compound 13 exhibited certain PCSK9-LDLR PPI inhibitory activity (IC50: 7.57 ± 1.40 μM). The direct binding affinity between 13 and PCSK9 was determined with a K D value of 2.50 ± 0.73 μM. The LDLR uptake function could be also restored to a certain extent by 13 in HepG2 cells. This well-characterized hit compound will facilitate the further development of novel small molecule inhibitors of PCSK9-LDLR PPI.

A number of novel small molecules, safrole oxide derivatives 4a-c, 6a-c, 9a-h, were synthesized by the reaction of safrole oxide with anilines 3 and 5, or its alkyl allyl ether derivative 7 with alkyl bromide 8 in moderate yields. The antiproliferative effects of all the target molecules on A549 cell growth were investigated and it was found that the 14 novel compounds could suppress A549 lung cancer cell growth. Among them, compound 6b was the most effective compound in inhibiting the proliferation of A549 cells.

An efficient process for the synthesis of N-azaaryl anilines via Smiles rearrangement as a tool. A variety of Nazaaryl anilines were generated by the reaction of substituted phenols, substituted anilines, aminopyridines and chloroacetyl chloride or pyridols, under base condition in good to excellent yields.

Stereoselective Synthesis of Arylglycine Derivatives via Palladium-Catalyzed -Arylation of a Chiral Nickel(II) Glycinate. -Structurally diverse aryl bromides are well tolerated in the -arylation reaction with a chiral nickel(II) glycinate complex. The diastereoisomerically pure nickel(II) arylglycine complexes can be converted to non-naturally occurring arylglycines in high yields and enantiomeric excess. The chiral auxiliary can be recovered and reused. -(ZHANG, F.; SUN, H.; SONG, Z.; ZHOU, S.; WEN, X.; XU, Q.-L.; SUN*, H.; J. Org. Chem. 80 (2015) 9, 4459-4464, http://dx.doi.org/10.