Recent Advancements in Pyrrole Synthesis

This review article features selected examples on the synthesis of functionalized pyrroles that were reported between 2014 and 2019. Pyrrole is an important nitrogen-containing aromatic heterocycle that can be found in numerous compounds of biological and material significance. Given its vast importance, pyrrole continues to be an attractive target for the development of new synthetic reactions. The contents of this article are organized by the starting materials, which can be broadly classified into four different types: substrates bearing π-systems, substrates bearing carbonyl and other polar groups, and substrates bearing heterocyclic motifs. Brief discussions on plausible reaction mechanisms for most transformations are also presented

Access to harmonine, a chemical weapon of ladybird beetles

The synthesis of harmonine, a defense alkaloid from the harlequin ladybird is reported by three different routes. The preparation of several new analogs with the same molecular weight and the decoration of gold nanoparticles with harmonines are also part of the present communication

Copper(I)-Catalyzed Synthesis of Unsymmetrical All-Carbon Bis-Quaternary Centers at the Opposing α-Carbons of Cyclohexanones

We describe a new synthetic reaction that generates all-carbon bis-quaternary centers at the opposing side of α-carbons in cyclohexanone with four different substituents in a controlled manner. Catalyzed by Cu(MeCN)BF salt, this chemistry is proposed to proceed via an intermediacy of unsymmetrical -allyl oxyallyl cations, which undergo a sequence of regioselective nucleophilic addition with substituted indoles and diastereoselective Claisen rearrangement in a single synthetic operation. The stereochemical outcome of the products features the diastereorelationship between the two aryl groups at the α,α\u27-positions

Nitrosporeusine analogue ameliorates Chandipura virus induced inflammatory response in CNS via NFκb inactivation in microglia.

Chandipura Virus (CHPV), a negative-stranded RNA virus belonging to the Rhabdoviridae family, has been previously reported to bring neuronal apoptosis by activating several factors leading to neurodegeneration. Following virus infection of the central nervous system, microglia, the ontogenetic and functional equivalents of macrophages in somatic tissues gets activated and starts secreting chemokines, thereby recruiting peripheral leukocytes into the brain parenchyma. In the present study, we have systemically examined the effect of CHPV on microglia and the activation of cellular signalling pathways leading to chemokine expression upon CHPV infection. Protein and mRNA expression profiles of chemokine genes revealed that CHPV infection strongly induces the expression of CXC chemokine ligand 10 (CXCL10) and CC chemokine ligand 5 (CCL5) in microglia. CHPV infection triggered the activation of signalling pathways mediated by mitogen-activated protein kinases, including p38, JNK 1 and 2, and nuclear factor κB (NF-kappaB). CHPV-induced expression of CXCL10 and CCL5 was achieved by the activation of p38 and NF-kappaB pathways. Considering the important role of inflammation in neurodegeneration, we have targeted NF-kappaB using a newly synthesised natural product nitrosporeusine analogue and showed incapability of microglial supernatant of inducing apoptosis in neurons after treatment

Nitrosporeusine inhibits CHPV induced microglia activation and reduces inflammatory molecules.

<p>A). CBA analysis was done from N9 supernatant and mouse brain protein to analyse expression level of cytokines. TNF-a, CCL2 and IL-6 shows enhanced expression in supernatant (6hpi) of N9. Our data suggest treatment of cells with (-)-25b compound is effective in inhibiting microglia mediated inflammation. Similarly, <i>in vivo</i> validation was performed in mouse brain (2dpi) and data was concomitant with in vitro result. B). Immunofluorescence staining for Iba-1 shows activated morphology of microglia. The star shaped morphology was more prominent in CHPV infected samples. The (-)-25b treated group shows decrease in activated morphology of microglia. C). ROS level using DCFDA shows decrease level in (-)-25b treated samples as compared to CHPV treated samples. NO generation was measured from N9 cells using Griess reagent. NO was measured from N9 supernatant shows increase level of NO in CHPV infected samples as compared to (-)-25b treated group at 6 hpi. D). Western blot analysis of Cox-2 and iNOS shows decrease expression level in (-)-25b treated group in in vitro as well as in vivo samples which was found to be upregulated in CHPV infected group.</p

CHPV induces microglial activation through NF-kappaB pathway.

<p>A). p38 (SB239063), JNK (SP600125), Dexamethasone (Dexa) an inhibitor of NF-kappaB was used at concentration of 10μm to check their effect on CHPV induced cytokines and chemokines production. CBA analysis of cytokines expression shows decrease in expression level in Dexa treated inhibitors whereas other inhibitors were not very effective. Though SB239063 showed significance decrease in CCL2, but was not effective in downregulating TNF-α and IL-6. B). Chemokine expression level was checked in presence of inhibitors. Dexa was found to be most effective in inhibiting chemokine expression. C) CBA was performed in presence of inactivated virus to asses if live virus is required for virus dependent inflammation. CBA data shows incapability of inactivated virus in inducing cytokine expression. D). Western blot experiment shows role of Akt phosphorylation in activation of NF-kappaB. The data shows treatment of PI3K inhibitor (LY294002) at 10μM inhibited p-Akt level and thus NF-kappaB was inhibited.</p

Nitrosporeusine analogue ameliorates Chandipura virus induced inflammatory response in CNS via NFκb inactivation in microglia - Table 1

<p>Nitrosporeusine analogue ameliorates Chandipura virus induced inflammatory response in CNS via NFκb inactivation in microglia</p> - Table