Tin(II) triflate Catalysed Synthesis of 3‐Methyleneisoindolin‐1‐ones

Abstract

We delineate a simple and straightforward tin(II) triflate catalyzed facile protocol for the synthesis of 3‐methyleneisoindolin‐1‐ones that applied to broad range of substrates, which simultaneously offers the functional group tolerance of the reaction and the stability of these scaffolds to the reaction conditions. In addition, in situ reduction of the exocyclic double bond in 3‐methyleneisoindolin‐1‐ones using PMHS is also reported.

A lesson for the maestro of the replication fork: Targeting the protein‐binding interface of proliferating cell nuclear antigen for anticancer therapy

“…Apart from it, we also answered some fundamental questions revolving around the functioning and subtle structural aspects of sliding proteins in T4 bacteriophage 45 . In the present study, we analyzed the binding ability of in‐house synthesized molecules consisting of 3‐methylenisoindolin‐1‐one scaffolds 26 . The 3‐methylenisoindolin‐1‐one is a prime scaffold found in various bioactive and pharmaceutical molecules that are used to develop anti‐inflammatory, anaesthetics, antipsychotic, and antiviral drugs 46,47 .…”

“…45 In the present study, we analyzed the binding ability of in-house synthesized molecules consisting of 3-methylenisoindolin-1-one scaffolds. 26 The 3-methylenisoindolin-1-one is a prime scaffold found in various bioactive and pharmaceutical molecules that are used to develop anti-inflammatory, anaesthetics, antipsychotic, and antiviral drugs. 46,47 We used a combination of various high-end computational techniques consisting of docking, conventional and steered MD simulations, MM-PBSA calculations, and enhanced umbrella sampling simulations to compare and rank the in-house synthesized compounds with standard inhibitor I1.…”

“…28 The 3D structure of standard inhibitor/molecule (I1) 25 was obtained from the PubChem database. A library of 3-methylenisoindolin-1-one molecules in SDF format 26 for molecular docking and further for computational analysis was prepared by Discovery Studio. DFT energy minimization protocols (B3LYP with a 6-31 + G(d,p) basic set) of Gaussian 16 29 were used to optimize ligand geometries.…”

“…25 These compounds were computationally shown to target the dimer interface of PCNA. In the present study, we explored the binding of molecule I1 (N′-[(2-hydroxy-1naphthyl) methylene]−1H-pyrazole-5-arbohydrazide) and identified lead molecules from the in-house synthesized library of 3-methylenisoindolin-1-one molecules 26 to target PCNA. The main objectives of the present work were to compare the binding of I1 molecule between the hydrophobic pocket and dimer interface of PCNA.…”

Novel 3-Methyleneisoindolinones Diversified via Intramolecular Heck Cyclization Induce Oxidative Stress, Decrease Mitochondrial Membrane Potential, Disrupt Cell Cycle, and Induce Apoptosis in Head and Neck Squamous Cell Carcinoma Cells

“…Inspired by our previous research study to synthesize 3-methyleneisoindolinone and considering the above findings, herein, we utilize a tin(II) triflate (Sn(OTf) 2 )-catalyzed reaction of 2-acetylcarboxylic ( 1 ) acid with substituted primary amines ( 2a – 2p ) for the synthesis of 3-methyleneisoindolin-1-ones ( 3a – 3p ) in 47–98% yields. 22 In extension to this approach, we further subjected three synthesized 3-methyleneisoindolinones to intramolecular Heck cyclization reactions to obtain five- to seven-membered ring products. Synthesis of a series of 19 examples of highly structurally diverse 3-methyleneisoindolinones was achieved using substituted primary amines such as −Ar, −(Het)Ar, −Bn, and (Het)Bn.…”