Protic Reaction Media for Nucleophilic Substitution Reactions

This chapter deals with the unusual substitution reactions in non-aprotic solvent. Selective protic solvents that are widely being accepted for nucleophilic substitution reactions not only enhance the reaction rate but also give desire for selectivity of substituted product. Protic solvents such as tert-alcohol, primary alcohol, ionic liquids with tert-alcohol and primary alcohol functionality, and bis-cationic ionic liquid with protic functionality were shown best result in substitution reactions. Aliphatic nucleophilic substitution significantly developed in protic reaction medium due to the hydrogen bonding interaction with leaving groups and nucleophile. The development of substitution reactions from past two decades are summarised in this book chapter

Therapeutic Outcomes of Isatin and Its Derivatives against Multiple Diseases: Recent Developments in Drug Discovery

Isatin (1H indole 2, 3-dione) is a heterocyclic, endogenous lead molecule recognized in humans and different plants. The isatin nucleus and its derivatives are owed the attention of researchers due to their diverse pharmacological activities such as anticancer, anti-TB, antifungal, antimicrobial, antioxidant, anti-inflammatory, anticonvulsant, anti-HIV, and so on. Many research chemists take advantage of the gentle structure of isatins, such as NH at position 1 and carbonyl functions at positions 2 and 3, for designing biologically active analogues via different approaches. Literature surveys based on reported preclinical, clinical, and patented details confirm the multitarget profile of isatin analogues and thus their importance in the field of medicinal chemistry as a potent chemotherapeutic agent. This review represents the recent development of isatin analogues possessing potential pharmacological action in the years 2016–2020. The structure–activity relationship is also discussed to provide a pharmacophoric pattern that may contribute in the future to the design and synthesis of potent and less toxic therapeutics

Anti-tuberculosis treatment-induced Drug Rash with Eosinophilia and Systemic Symptoms syndrome

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a life-threatening adverse drug reaction that is distinct from other drug-related reactions. We report a rare case of DRESS syndrome following anti-tuberculosis treatment

Sweetening Pharmaceutical Radiochemistry by 18F-Fluoroglycosylation: Recent Progress and Future Prospects

In the field of 18F-chemistry for the development of radiopharmaceuticals for positron emission tomography (PET), various labeling strategies by the use of prosthetic groups have been implemented, including chemoselective 18F-labeling of biomolecules. Among those, chemoselective 18F-fluoroglycosylation methods focus on the sweetening of pharmaceutical radiochemistry by offering a highly valuable tool for the synthesis of 18F-glycoconjugates with suitable in vivo properties for PET imaging studies. A previous review covered the various 18F-fluoroglycosylation methods that were developed and applied as of 2014 (Maschauer and Prante, BioMed. Res. Int. 2014, 214748). This paper is an updated review, providing the recent progress in 18F-fluoroglycosylation reactions and the preclinical application of 18F-glycoconjugates, including small molecules, peptides, and high-molecular-weight proteins

Nucleophilic Radiofluorination Using Tri-<i>tert</i>-Butanol Ammonium as a Bifunctional Organocatalyst: Mechanism and Energetics

We present a quantum chemical analysis of the 18F-fluorination of 1,3-ditosylpropane, promoted by a quaternary ammonium salt (tri-(tert-butanol)-methylammonium iodide (TBMA-I) with moderate to good radiochemical yields (RCYs), experimentally observed by Shinde et al. We obtained the mechanism of the SN2 process, focusing on the role of the –OH functional groups facilitating the reactions. We found that the counter-cation TBMA+ acts as a bifunctional promoter: the –OH groups function as a bidentate ‘anchor’ bridging the nucleophile [18F]F− and the –OTs leaving group or the third –OH. These electrostatic interactions cooperate for the formation of the transition states of a very compact configuration for facile SN2 18F-fluorination

Cyclization mechanism of phomopsene synthase : mass spectrometry based analysis of various site-specifically labeled terpenes

Elucidation of the cyclization mechanism catalyzed by terpene synthases is important for the rational engineering of terpene cyclases. We developed a chemoenzymatic method for the synthesis of systematically deuterium-labeled geranylgeranyl diphosphate ( GGPP), starting from site-specifically deuterium-labeled isopentenyl diphosphates (IPPs) using IPP isomerase and three prenyltransferases. We examined the cyclization mechanism of tetracyclic diterpene phomopsene with phomopsene synthase. A detailed EI-MS analysis of phomopsene labeled at various positions allowed us to propose the structures corresponding to the most intense peaks, and thus elucidate a cyclization mechanism involving double 1,2-alkyl shifts and a 1,2-hydride shift via a dolabelladien-15-yl cation. Our study demonstrated that this newly developed method is highly sensitive and provides sufficient information for a reliable assignment of the structures of fragmented ions

Synthesis and characterization of highly ordered nanosized PbS thin films: modified silar

In the current status, we have successfully synthesized lead sulfide (PbS) thin films using a modified successive ionic layer absorption and reaction (SILAR) method. The synthesized film was characterized using UV-Vis-NIR spectrophotometer, X-ray diffraction (XRD) and field emission scanning electron microscopy (FESEM) techniques for optical, structural and morphological properties. Opto-structural study demonstrates that synthesized thin film has a pure crystal structure. The surface morphology study indicates a nanospherical surface morphology without pinhole on the substrate surfaces. Overall study clearly demonstrates that the synthesized PbS thin film by SILAR method have great potential for sensitization of oxide microstructure.clos

Sequential Enzymatic Epoxidation Involved in Polyether Lasalocid Biosynthesis

Enantioselective epoxidation followed by regioselective epoxide opening reaction are the key processes in construction of the polyether skeleton. Recent genetic analysis of ionophore polyether biosynthetic gene clusters suggested that flavin-containing monooxygenases (FMOs) could be involved in the oxidation steps. In vivo and in vitro analyses of Lsd18, an FMO involved in the biosynthesis of polyether lasalocid, using simple olefin or truncated diene of a putative substrate as substrate mimics demonstrated that enantioselective epoxidation affords natural type mono- or bis-epoxide in a stepwise manner. These findings allow us to figure out enzymatic polyether construction in lasalocid biosynthesis