Kinetic resolution of ß-ketoesters with quaternary stereocenters via a carbene-catalyzed benzoin reaction.

Chiral ß-ketoesters bearing fully substituted carbon centers are important building blocks in organic synthesis. Mono-substituted ketoesters have been widely used to synthesize the above compounds through asymmetric additions or substitutions. The limitations of these protocols mainly exist in the substrate scopes, and α-methyl or α-fluoro-substituted ß-ketoesters or acetyl acetates are frequently used owing to their relatively higher reactivity. To break through this limitation, we employed N-heterocyclic carbene-catalyzed kinetic resolution to achieve the access to enantioenriched ß-ketoesters with quaternary stereocenters. Sterically more bulky groups such as benzyl, allyl, phenyl and cyclopropyl groups are all tolerated using this method.

One-pot synthesis of tetrazole-1,2,5,6-tetrahydronicotinonitriles and cholinesterase inhibition: Probing the plausible reaction mechanism via computational studies.

In the present study, one-pot synthesis of 1H-tetrazole linked 1,2,5,6-tetrahydronicotinonitriles under solvent-free conditions have been carried out in the presence of tetra-n-butyl ammonium fluoride trihydrated (TBAF) as catalyst and solvent. Computational studies have been conducted to elaborate two plausible mechanistic pathways of this one-pot reaction. Moreover, the synthesized compounds were screened for cholinesterases (acetylcholinesterase and butyrylcholinesterase) inhibition which are consider to be major malefactors of Alzheimer's disease (AD) to find lead compounds for further research in AD therapy.

Synthesis, biological evaluation and molecular docking of N-phenyl thiosemicarbazones as urease inhibitors.

Urease is an important enzyme which breaks urea into ammonia and carbon dioxide during metabolic processes. However, an elevated activity of urease causes various complications of clinical importance. The inhibition of urease activity with small molecules as inhibitors is an effective strategy for therapeutic intervention. Herein, we have synthesized a series of 19 benzofurane linked N-phenyl semithiocarbazones (3a-3s). All the compounds were screened for enzyme inhibitor activity against Jack bean urease. The synthesized N-phenyl thiosemicarbazones had varying activity levels with IC50 values between 0.077 ± 0.001 and 24.04 ± 0.14 µM compared to standard inhibitor, thiourea (IC50 = 21 ± 0.11 µM). The activities of these compounds may be due to their close resemblance of thiourea. A docking study with Jack bean urease (PDB ID: 4H9M) revealed possible binding modes of N-phenyl thiosemicarbazones.