Girijesh Kumar Verma

Molecular Docking and in Vitro Antileishmanial Evaluation of Chromene-2-thione Analogues.

Leishmaniases are an epidemic in various countries, and the parasite is developing resistance against available drugs. Thus, development of new drugs against Leishmania is an open area of investigation for synthetic organic chemists. To meet this challenge, a series of chromene-2-thione derivatives have been synthesized and docked into the active site of trypanothione reductase (TryR) enzyme required for redox balance of the parasite. These were screened on promastigote, axenic amastigote, and intracellular amastigote stages of Leishmania donovani and found to show high levels of antileishmanial activity together with minimal toxicity to human peripheral blood mononuclear cells. Compounds 3b and 3k were found to be the most active among the tested compounds. Although the compounds show moderate antileishmanial activity, they identify a chemical space to design and develop drugs based on these chromene-2-thione derivatives against the Leishmania parasite.

4-Dimethylamino pyridine-promoted one-pot three-component regioselective synthesis of highly functionalized 4H-thiopyrans via heteroannulation of β-oxodithioesters.

A highly convergent and regioselective heteroannulation protocol for the synthesis of hitherto unreported highly substituted 2-amino-4-(aryl/alkyl)-5-(aroyl/heteroaroyl)-3-(cyano/carboalkoxy)-6-methylthio-4H-thiopyran derivatives has been developed. This one-pot three-component domino coupling of β-oxodithioesters, aldehydes, and malononitrile/ethyl or methyl cyanoacetate is promoted by 4-dimethylamino pyridine (DMAP) in solvent (dichloromethane (DCM)) as well as under solvent-free conditions. Systematic optimization of reaction parameters identified that the three-component coupling (3CC) protocol is tolerant to a wide array of functionality providing densely functionalized 4H-thiopyrans in excellent yields. The merit of this cascade Knoevenagel condensation/Michael addition/cyclization sequence is highlighted by its high atom-economy, excellent yields, and efficiency of producing three new bonds (two C-C and one C-S) and one stereocenter in a single operation.

Catalyst-free one-pot four-component domino reactions in water–PEG-400: highly efficient and convergent approach to thiazoloquinoline scaffolds

A cost-effective and eco-friendly straightforward synthesis of highly diversified thiazoloquinoline scaffolds is successfully achieved via one-pot four-component cascade reaction utilizing α-enolic dithioesters, cysteamine, aldehydes, and cyclic 1,3-diketones in water–PEG-400. The new efficient domino protocol generates two rings by the concomitant formation of C–C (two), C–N (two), and C–S multiple bonds presumably involving a sequence of N,S-acetal formation, Knoevenagel reaction, aza–ene reaction, imine–enamine/keto–enol tautomerization, and N-cyclization as key steps. The merit of this protocol is highlighted by its easily available and economical starting materials, operational simplicity, efficient utilization of all the reactants, clean reaction profile, simple workup procedure, and tolerance of a wide variety of functional groups.

InCl3 catalyzed domino route to 2H-chromene-2-ones via [4 + 2] annulation of 2-hydroxyarylaldehydes with α-oxoketene dithioacetal under solvent-free conditions

A facile and efficient synthesis of 3-aroyl/heteroaroyl/ferrocenoyl/alkanoyl-2H-chromen-2-ones has been developed by the cyclocondensation of α-oxoketene dithioacetals and 2-hydroxyarylaldehydes catalyzed by InCl3 under solvent-free conditions. No co-catalyst or activator is needed and MeSH is the only by-product of this protocol. The methodology involves ring annulation of 2-hydroxyarylaldehydes with a variety of α-oxoketene dithioacetals offering rapid entry into differentially substituted chromen-2-ones. The condensation of ferrocene derived α-oxoketene dithioacetal and 2-hydroxyarylaldehyde furnished coumarin installed on a ferrocene platform.

Eco-efficient, regioselective and rapid access to 4,5-disubstituted 1,2,3-thiadiazoles via [3 + 2] cycloaddition of α-enolicdithioesters with tosyl azide under solvent-free conditions

An efficient, sustainable, and regioselective one-pot synthesis of hitherto unreported 4-aroyl/hetaroyl/alkanoyl-5-alkyl/allyl/benzylsulfanyl-1,2,3-thiadiazoles has been achieved by [3 + 2] cycloaddition of α-enolicdithioesters with tosyl azide through cascade 1–2 (S–N) and 3–4 (C–N) bond connections involving Wolff-type heterocyclization. Optimally, the reactions are very fast and completed within 2–15 minutes, when a mixture of α-enolicdithioester and tosyl azide was stirred at 0 °C in the presence of Et3N under solvent-free conditions. Furthermore, no co-catalyst or activator is necessary. The eco-compatibility, mild conditions, excellent yields, easy purification, and avoidance of expensive/toxic reagents are advantages of this protocol to access this medicinally privileged substructure.

Construction of five- and six-membered heterocycles on both Cp rings of the ferrocene moiety of α-oxoketene-S,S-acetal and β-oxodithioester via heteroaromatic annulation

1,1′-Bis(1,1-dimethylsulfanyl-3-oxo-1-propene)ferrocene and 1,1′-Bis(methyl-3-hydroxy-prop-2-ene-dithioate)ferrocene have been shown to be useful three-carbon synthons for the efficient synthesis of hitherto unreported and synthetically demanding Fc-heterocycles. Five-membered (pyrazole, isoxazole, and thiophene) and six-membered (pyrimidine, coumarin, and quinoline) heterocycles have been constructed on both Cp rings of the ferrocene matrix via regioselective heteroaromatic annulation.

DMAP mediated one-pot domino thienannulation: a versatile, regioselective and green mechanochemical route to naphtho[2,3-b]thiophenes

Solvent-free mechanochemical route to naphtho[2,3-b]thiophenes via [3 + 2] oxidative heteroannulation of α-enolicdithioesters and β-oxothioamides with 1,4-naphthoquinone has been achieved at room temperature.

DMAP-promoted domino annulation of β-ketothioamides with internal alkynes: a highly regioselective access to functionalized 1,3-thiazolidin-4-ones at room temperature

DMAP-mediated rapid and efficient one-pot regioselective access to functionalized 1,3-thiazolidin-4-ones via annulation of β-ketothioamides with internal alkynes has been achieved under mild reaction conditions. The merit of this straightforward domino protocol is highlighted by its operational simplicity, short reaction time, tolerance of a large variety of functional groups, and efficiency of producing two new bonds (C–S and C–N) and one thiazolidine ring.