Complementary routes to both enantiomers of pipecolic acid and 4,5-dihydroxypipecolic acid derivatives

Complementary new routes to both enantiomers of N-protected pipecolic acid and the corresponding 4,5-dihydroxylated derivatives are developed, which involve stereo-divergent allylation of a chiral N-allylimine and ring-closing metathesis as key steps.     

A stereo-divergent route to aminocyclopentitol derivatives

A stereo-divergent synthetic strategy based on diastereoselective vinylation of an α-amino aldehyde, ring-closing metathesis reaction and diastereoselective dihydroxylation reaction as key steps has been developed for the synthesis of three aminocyclopentitol derivatives of chemical and biological relevance.     

Drug Design,Synthesis and Biological Evaluation of Heterocyclic Molecules as Anti-Inflammatory Agents

Non-steroidal anti-inflammatory drugs (NSAIDs) are generally utilized for numerous inflammatory ailments. The long-term utilization of NSAIDs prompts adverse reactions such as gastrointestinal ulceration, renal dysfunction and hepatotoxicity; however, selective COX-2 inhibitors prevent these adverse events. Various scientific approaches have been employed to identify safer COX-2 inhibitors, as in any case, a large portion of particular COX-2 inhibitors have been retracted from the market because of severe cardiovascular events. This study aimed to develop and synthesize a novel series of indomethacin analogues with potential anti-inflammatory properties and fewer side effects, wherein carboxylic acid moiety was substituted using DCC/DMAP coupling. This study incorporates the docking of various indomethacin analogues to detect the binding interactions with COX-2 protein (PDB ID: 3NT1). MD simulation was performed to measure the stability and flexibility of ligand–protein interactions at the atomic level, for which the top-scoring ligand–protein complex was selected. These compounds were evaluated in vitro for COX enzymes inhibition. Likewise, selected compounds were screened in vivo for anti-inflammatory potential using the carrageenan-induced rat paw oedema method and their ulcerogenic potential. The acute toxicity of compounds was also predicted using in silico tools. Most of the compounds exhibited the potent inhibition of both COX enzymes; however, 3e and 3c showed the most potent COX-2 inhibition having IC50 0.34 µM and 1.39 µM, respectively. These compounds also demonstrated potent anti-inflammatory potential without ulcerogenic liability. The biological evaluation revealed that the compound substituted with 4-nitrophenyl was most active.     

Stability-Indicating HPTLC Method for Analysis of Moclobemide, and Use of the Method to Study Degradation Kinetics

A sensitive, selective, precise, and stability-indicating HPTLC method for analysis of moclobemide in the bulk drug and in formulations has been established and validated. Aluminium TLC plates precoated with silica gel 60 F₂₅₄ were used with benzene–methanol–40% ammonia 7:3:0.1 (v/v) as mobile phase. Densitometric analysis was performed in absorbance mode at 238 nm. Compact bands were obtained for moclobemide (R _F 0.67 ± 0.02; n = 6). The drug was subjected to acidic and alkaline hydrolysis, oxidation, dry heat treatment, and photodegradation. The drug undergoes degradation under acidic, basic, and oxidising conditions. The degradation products were well resolved from the pure drug with significantly different R _F values, so the method can be regarded as stability-indicating. Response to moclobemide was a linear function of amount in the range 50–600 ng per band, with a correlation coefficient, r ², of 0.9967 ± 0.51. LOD and LOQ, determined experimentally, were 10 and 30 ng per band, respectively. Statistical analysis proves the method is repeatable and specific for analysis of moclobemide. The method was used to investigate the kinetics of alkaline degradation. The Arrhenius plot was constructed and the activation energy calculated.     

Synthesis of oxepine-, oxocine- and azepine-annulated carbazole derivatives by combined Claisen rearrangement and diene/enyne metathesis

A new route to various medium ring heterocycle-annulated tetra-, penta- and hexacyclic carbazole derivatives has been developed using successive applications of three atom economic processes, viz. Claisen rearrangement, olefin metathesis and Diels-Alder reactions.     

Stereoselective synthesis of 2-azetidinylglycine and aminopyrrolidone derivatives from Garner’s aldehyde

A new route to two hitherto unknown 2-azetidinylglycine derivatives and an aminopyrrolidone derivative has been developed which featured a diastereoselective conjugate addition of benzyl amine to an α,β-unsaturated ester derived from Garner’s aldehyde as the key step.     

Enantiodivergent synthesis of N-protected azetidine-2-carboxylic acid

A new route to both enantiomers of N-tosyl-azetidine-2- carboxylic acid has been developed from (R)-2-cyclohexylideneglyceraldehyde which proceeded with good overall yield and excellent enantiomeric purity.     

Unified Approach to the Asymmetric Synthesis of Higher Homologues of (3-Quinolyl)-alanine

A new protocol based on a palladium-catalyzed Heck reaction of an amino acid–derived vinyl unit with 3-bromoquinoline has been developed to access the title compounds in good yield and optical purity.     

Synthesis of spiro-fused heterocycles under aerobic conditions by using polymer gel-entrapped catalyst

Research on Chemical Intermediates - An expedient synthesis of spiro-fused heterocycles from multi-component reaction of urea, aryl aldehydes and Meldrum’s or barbituric acid by using polymer...