Studies on the reaction of aziridines with nitriles and carbonyls: synthesis of imidazolines and oxazolidines

Reaction of N-tosylaziridines with nitriles and carbonyls to produce imidazolines and oxazolidines has been studied in the presence of a variety of Lewis acids. The reaction is efficient with 1 equiv of BF3.Et2O or Et3OBF4 in CH2Cl2. However, it is catalytic with metal triflates that give the best results for cycloaddition of N-tosylaziridine with nitriles under solvent free conditions. The same reaction with carbonyls proceeds best in CH2Cl2 in the presence of molecular sieves. Among various triflates, Zn(OTf)2 has been found to be the best. The cleavage of the N-Ts bond of the cyclized products has been studied in order to make it more versatile in synthesis. The mechanistic aspect of the reaction has been studied by using chiral aziridines as substrates. These formal [3+2] cycloaddition reactions of aziridines with nitriles and carbonyls proceed in a Ritter fashion.     

S-oxidation of thiazolidinedione with hydrogen peroxide, peroxynitrous acid, and C4a-hydroperoxyflavin: a theoretical study

Quantum chemical analysis was carried out to model metabolism of glitazone class of drugs through oxygen transfer process to the sulfur atom of thiazolidinedione ring with different oxidants such as H(2)O(2), HOONO, and C4a-hydroperoxyflavin. Complete optimization (geometric and energy parameters) of all the required structures and transition states on the reaction path was carried out using MP2(full)/6-31+G(d,p). Charge and second-order delocalization analyses of important structures were carried out using the NBO method. The effect of solvent on the oxygen transfer to sulfur of thiazolidinedione was studied by including one, two, or three explicit water molecules. These calculations revealed that explicit solvent (water) effectively contributed in the sulfoxidation of thiazolidinedione and led to remarkable reduction in the energy barrier by ～10 kcal/mol as compared to the gas phase. These results were found to be consistent with previously reported S-oxidation of dimethyl sulfide. When explicit water molecules were included, solvent molecules stabilize the charge separation at the transition state via specific interactions, and oxidation occurs via stretching of the O-O bond of oxidants and gradual formation of S-O bond. This study is helpful in understanding the metabolite generation due to the S-oxidation process in the glitazone series of antidiabetic drugs under physiological conditions.     

Synthesis and Characterization of Photoactive Amphiphilic Polymers

We have synthesized light sensitive nano micelles for their applications as drug delivery agents. Various azo compounds having different dipole moment values have been covalently attached to an amphiphilic pegylated co‐polymer and their light sensitive behavior has been studied in both aqueous and organic media with ultra violet light to understand the light dependent supramolecular organization.     

Design and Lipase Catalyzed Synthesis of 4-Methylcoumarin-siloxane Hybrid Copolymers

Poly dimethylsiloxanes with amino end groups were copolymerized with diesters of 4-methylcoumarins enzymatically using a lipase (Candida antarctica lipase) as a biocatalyst. In a separate synthesis, 4-methylcoumarin was also incorporated into the poly siloxanes-isophthalate copolymers by functionalization of hydroxyl groups in the isophthalate moiety. The synthesis and characterization of two sets of novel copolymers are presented. The thermal and flammability properties of these polymers have also been studied using TGA and microcalorimetry, respectively.     

Large‐scale separation of antipsychotic alkaloids from Rauwolfia tetraphylla L. by pH‐zone‐refining fast centrifugal partition chromatography

pH‐zone‐refining centrifugal partition chromatography was successively applied in the large‐scale separation of close R_f antipsychotic indole alkaloids directly from CHCl₃ fraction of Rauwolfia tetraphylla leaves. Two experiments with increasing mass from 500 mg to 3 g of crude alkaloid extracts ( 1 C) of R. tetraphylla were carried out in normal‐displacement mode using a two‐phase solvent system composed of methyl tert‐butyl ether/ACN/water (4:1:5, v/v/v) where HCl (12 mM) was added to the lower aqueous stationary phase as a retainer and triethylamine (5 mM) to the organic mobile phase as an eluter. The two centrifugal partition chromatography separations afforded a total of 162.6 mg of 10‐methoxytetrahydroalstonine ( 1 ) and 296.5 mg of isoreserpiline ( 2 ) in 97% and 95.5% purity, respectively, along with a 400.9 mg mixture of α‐yohimbine and reserpiline ( 3 and 4 ). Further, this mixture was resolved over medium pressure LC using TLC grade silica gel H (average particle size 10 μm), which afforded 160.4 mg of α‐yohimbine ( 3) and 150.2 mg of reserpiline ( 4) in >95% purities. The purity of the isolated antipsychotic alkaloids was analyzed by high‐performance LC and their structures were characterized on the basis of their 1D, 2D NMR and electrospray ionization‐mass spectroscopic data.     

Bis(thiophen-2-yl-methylene) Benzene-1, 4-Diamine as Fluorescent Probe for the Detection of Fe3+ in Aqueous Samples

Journal of Fluorescence - A Schiff base bis(thiophen-2-yl-methylene)benzene-1, 4-diamine (L) was synthesized and used for selective and sensitive detection of Fe3+. L exhibited enhanced...     

Identifying structural–functional analogue of GRL0617, the only well-established inhibitor for papain-like protease (PLpro) of SARS-CoV2 from the pool of fungal metabolites using docking and molecular dynamics simulation

Molecular Diversity - The non-structural protein (nsp)-3 of SARS-CoV2 coronavirus is sought to be an essential target protein which is also named as papain-like protease (PLpro). This protease...     

Curse of La Corona: unravelling the scientific and psychological conundrums of the 21st century pandemic

Molecular Diversity - Microbes possess a tremendous potential to interact with their surroundings and have continued to shape the future of all life forms existing on earth. Of all the groups of...     

In Silico Evaluation of Natural Flavonoids as a Potential Inhibitor of Coronavirus Disease

The recent coronavirus disease (COVID-19) outbreak in Wuhan, China, has led to millions of infections and the death of approximately one million people. No targeted therapeutics are currently available, and only a few efficient treatment options are accessible. Many researchers are investigating active compounds from natural plant sources that may inhibit COVID-19 proliferation. Flavonoids are generally present in our diet, as well as traditional medicines and are effective against various diseases. Thus, here, we reviewed the potential of flavonoids against crucial proteins involved in the coronavirus infectious cycle. The fundamentals of coronaviruses, the structures of SARS-CoV-2, and the mechanism of its entry into the host’s body have also been discussed. In silico studies have been successfully employed to study the interaction of flavonoids against COVID-19 M^pro, spike protein PL^pro, and other interactive sites for its possible inhibition. Recent studies showed that many flavonoids such as hesperidin, amentoflavone, rutin, diosmin, apiin, and many other flavonoids have a higher affinity with M^pro and lower binding energy than currently used drugs such as hydroxylchloroquine, nelfinavir, ritonavir, and lopinavir. Thus, these compounds can be developed as specific therapeutic agents against COVID-19, but need further in vitro and in vivo studies to validate these compounds and pave the way for drug discovery.