Prasanta Ray Bagdi

Copper oxide nanoparticle mediated ‘click chemistry’ for the synthesis of mono-, bis- and tris-triazole derivatives from 10,10-dipropargyl-9-anthrone as a key building block

The synthesis of mono-, bis- and tris-triazole derivatives was accomplished using 10,10-dipropargyl-9-anthrone as a key starting material. Various acetylenic compounds (2–5) derived from 10,10-dipropargyl-9-anthrone on reaction with alkyl/benzyl bromides and sodium azide in the presence of 10 mol% of copper oxide nanoparticles along with 20 mol% sodium ascorbate in water afforded a wide variety of triazoles derivatives (8–13) under heating at 70 °C. The salient features of the present protocol are: mild reaction conditions, a shorter reaction time, the reusability of the catalyst, and its applicability with a wide range of substrates. Moreover, the mono-triazole 8b undergoes extended assembly in the solid state forming a zig-zag supramolecular structure stabilized by π–π and C–H⋯π interactions. Interestingly, the single crystal X-ray structure of 9b shows that it forms a supramolecular ball structure stabilized by a combination of C–H⋯O interaction and hydrogen bonding. Furthermore the presence of water molecules embedded in the crystal lattice of 9b allows these supramolecular balls to arrange in a chain generating a fascinating supramolecular architecture.

Synthesis of 2-triazolyl-imidazo[1,2-a]pyridine through a one-pot three-component reaction using a nano copper oxide assisted click-catalyst

The syntheses of 2-triazolyl imidazo[1,2-a]pyridine (8a–o) were accomplished through three component A3 coupling followed by 5-exo dig cyclisation by employing 1-alkyl-1,2,3-triazole-4-carbaldehyde, amidine and terminal alkynes using 5 mol% nanocopper oxide together with 10 mol% sodium ascorbate as a click-catalyst in ethanol at 70 °C. The present protocol was further utilized for the synthesis of 2-(2-triazolyl-imidazo[1,2-a]pyridin-3-yl)ethanol (9a–e). In addition, the molecular structure of 8c possesses a C–H⋯π interaction (H17b⋯C10) along with a peculiar supramolecular layered structure architecture. This protocol features ready recyclability of the catalyst, good yields and wide substrate scope. Moreover, the syntheses of triazolyl precursors (1-alkyl-1,2,3-triazol-4-yl)methanol (4a–f) have also been achieved through a nano copper oxide mediated click-catalyst in water at 70 °C.

Yb(OTf)3 catalysed regioselective synthesis of unusual di- and tri- substituted 3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one derivatives through a pseudo four-component hetero-Diels–Alder reaction

An efficient and facile regioselective synthesis of di- and tri- substituted 3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one derivatives was reported from 4-hydroxydithiocoumarin, ammonium acetate/primary amines and aldehydes involving a ytterbium triflate catalysed pseudo four component hetero-Diels–Alder reaction. The significant features of the present protocol are: mild reaction conditions, shorter reaction time, good yields, and unusual ring closure leading to the formation of C–C, C–N and C–S bonds in a single step operation.

Insights into the inhibitory mechanism of triazole-based small molecules on phosphatidylinositol-4,5-bisphosphate binding pleckstrin homology domain

Background Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is an important regulator of several cellular processes and a precursor for other second messengers which are involved in cell signaling pathways. Signaling proteins preferably interact with PI(4,5)P2 through its pleckstrin homology (PH) domain. Efforts are underway to design small molecule-based antagonist, which can specifically inhibit the PI(4,5)P2/PH-domain interaction to establish an alternate strategy for the development of drug(s) for phosphoinositide signaling pathways. Methods Surface plasmon resonance, molecular docking, circular dichroism, competitive Förster resonance energy transfer, isothermal titration calorimetric analyses and liposome pull down assay were used. Results In this study, we employed 1,2,3-triazol-4-yl methanol containing small molecule (CIPs) as antagonists for PI(4,5)P2/PH-domain interaction and determined their inhibitory effect by using competitive-surface plasmon resonance analysis (IC50 ranges from 53 to 159 nM for PI(4,5)P2/PLCδ1-PH domain binding assay). We also used phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3], phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2], PI(4,5)P2 specific PH-domains to determine binding selectivity of the compounds. Various physicochemical analyses showed that the compounds have weak affect on fluidity of the model membrane but, strongly interact with the phospholipase C δ1 (PLCδ1)-PH domains. The 1,2,3-triazol-4-yl methanol moiety and nitro group of the compounds are essential for their exothermic interaction with the PH-domains. Potent compound can efficiently displace PLCδ1-PH domain from plasma membrane to cytosol in A549 cells. Conclusions Overall, our studies demonstrate that these compounds interact with the PIP-binding PH-domains and inhibit their membrane recruitment. General significance These results suggest specific but differential binding of these compounds to the PLCδ1-PH domain and emphasize the role of their structural differences in binding parameters. These triazole-based compounds could be directly used/further developed as potential inhibitor for PH domain-dependent enzyme activity.

One-pot three-component regioselective synthesis of C1-functionalised 3-arylbenzo[f]quinoline

An efficient method for regioselective synthesis of C1-functionalised 3-arylbenzo[f]quinoline has been demonstrated via γ-selective aromatization using β-ketoester, 2-naphthylamine and aromatic aldehyde by employing 10 mol% camphorsulfonic acid as the catalyst in acetonitrile at 70 °C. In this approach, two C–C bond formations will result in functionalised benzo[f]quinoline in a one-pot three-component reaction. In addition, the present protocol has a diverse substrate scope with good yields. Furthermore, the protocol was directly utilised for the synthesis of alkyl 2-(3-(naphthalen-2-yl)benzo[f]quinolin-1-yl)acetate, allyl 2-(3-(heteroaromatic)benzo[f]quinolin-1-yl)acetate and functionalised 1,2,3-trisubstituted benzo[f]quinoline.