M. P. Kaushik

Imidazole-Catalyzed Monoacylation of Symmetrical Diamines

An imidazole-catalyzed protocol for monoacylation of symmetrical diamines has been developed. The protocol gave selective monoacylation of aliphatic (cyclic and acyclic) primary and secondary diamines. In the reaction, imidazole acts as both catalyst and a leaving group. Different monoacylated piperazines and other diamines were synthesized at room temperature in an ethanol/water solvent system.

Design, synthesis, and antimalarial evaluation of thiazole-derived amino acids

A series of thiazole-derived N-Boc amino acids were synthesized and evaluated as targeted potential antimalarials against plasmepsins II enzyme of malaria parasite Plasmodium falciparum. All the compounds showed moderate to good activity. Compounds 3f and 3g were found to have highest the 50% inhibitory concentration (IC50) values (3.45xa0μM and 4.89xa0μM, respectively) against Plasmodium falciparum. The compounds docked to the active site of plasmepsin II. Most of the compounds were found to interact with the catalytic amino acids ASP34 and ASP214 of plasmepsin II. A good correlation was observed between binding energy and antiparasitic activity of the thiazole derivatives.

Oviposition and flight orientation response of Aedes aegypti to certain aromatic aryl hydrazono esters

Aedes aegypti is a day-biting, highly anthropophilic mosquito and a potential vector of dengue and chikungunya in India. A. aegypti is a container breeder, generally oviposit in the stored and fresh water bodies, and discarded containers near residential areas that provide suitable habitats for oviposition by gravid females. The diurnal activity and endophilic nature of these mosquitoes have increased the frequency of contact with human being. Assured blood meal from human host in an infested area leads to increased disease occurrence. Gravid mosquitoes can potentially be lured to attractant-treated traps and could subsequently be killed with insecticides or growth regulators. In this direction, oviposition by A. aegypti females to aryl hydrazono esters (AHE)-treated bowls at 10xa0ppm concentration was tested in dual choice experiment, and their orientation response to these ester compounds was studied in Y-tube olfactometer. Among the esters tested, AHE-2, AHE-11 and AHE-12 elicited increased egg deposition with oviposition activity indices (OAI) of +0.39, +0.24 and +0.48, respectively, compared to control; in contrast, AHE-8, AHE-9 and AHE-10 showed negative oviposition response with OAI of −0.46, −0.35 and −0.29, respectively, at 10xa0mg/L. In the Y-tube olfactometer bioassay, AHE-2 attracted 60xa0% females compared to control, while to the odour of AHE-11 and AHE-12, about 70xa0% of the females were trapped in treated chambers. In contrast, only 27–30xa0% of gravid females entered the chamber releasing AHE-8, AHE-9 and AHE-10 odour plumes, while 70xa0% entered control chamber, evincing a possible non-preference of treatment odours as well as interference with olfactory receptors. These compounds have the potential for application as oviposition stimulants or deterrents for surveillance and control of mosquito population using ovitraps.

Synthesis and in vitro evaluation of xylene linked carbamoyl bis-pyridinium monooximes as reactivators of organophosphorus (OP) inhibited electric eel acetylcholinesterase (AChE).

A series of carbamoyl bis-pyridinium monooximes linked with xylene linker were synthesized and their in-vitro reactivation potential was evaluated against acetylcholinesterase (AChE) inhibited by organophosphorus inhibitors (OP) such as sarin, DFP and VX and the data were compared with reactivation obtained with 2-PAM and obidoxime. Amongst the synthesized compounds, 3-carbamoyl-2hydroxyiminomethyl-1-1-(1,4-phenylenedimethyl)-bispyridinium dibromide (5e) 3-carbamoyl-2hydroxyiminomethy l-1-1-(1,3-phenylenedimethyl)-bispyridinium dibromide (5k) and 4-carbamoyl-2hydroxyiminomethyl-1-1-(1,3-phenylenedimethyl)-bispyridinium dibromide (5l) were found to be the most potent reactivators for electric eel AChE inhibited by sarin and DFP. However, in case of VX inhibited AChE, none of the synthesized oximes could surpass the reactivation potential of 2-PAM and obidoxime. The pKa values of all the oximes were determined and correlated with their observed reactivation potential.

Titania nanomaterials: efficient and recyclable heterogeneous catalysts for the solvent-free synthesis of poly-substituted quinolines via Friedlander hetero-annulation

The present communication describes the use of titania (TiO2) nanomaterials of different sizes (16 nm, 35 nm, 70 nm, 200 nm, and 1000 nm) as heterogeneous catalysts for the preparation of a series of medicinally significant poly-substituted quinoline derivatives via Friedlander hetero-annulation. These TiO2 nanomaterials exhibited remarkable catalytic activity with a high substrate to catalyst molar ratio (20u2006:u20061) to achieve the synthetic targets in excellent yields ranging from 81–94%. The effect of catalyst particle size on the yield of the quinolines was also investigated. Yields of product were found to decrease when the TiO2 particle size increased from 16 nm to 1000 nm. GC-MS data indicated that TiO2 nanoparticles having 16 nm and 35 nm size of anatase phase provided better yields of the target compound, followed by particles of 70 nm in size, whereas 200 nm and 1000 nm size of anatase phase did not show the formation of the product under the same reaction conditions. The use of catalyst in solvent-free reaction conditions and its reusability up to five-cycles with similar catalytic response are the unique features of this heterogeneous catalysis. Furthermore, greater selectivity, cost-efficiency, clean reaction profiles, simple work-up procedure and high yield are the noteworthy features of this eco-friendly green protocol.

Efficient and Convenient One‐Pot Synthesis of Phosphoramidates and Phosphates

Abstract A simple and efficient one‐pot method is described for the synthesis of phosphoramidates/phosphates in excellent yields from dialkylphosphites and trichloroisocyanuric acid in acetonitrile and subsequent treatment with dialkyl amines/alcohols. The procedure is operationally simple, has reduced reaction times, and uses a one‐pot procedure.

CDI-mediated monoacylation of symmetrical diamines and selective acylation of primary amines of unsymmetrical diamines

A highly efficient and green protocol for monoacylation of symmetrical diamines and chemoselective acylation of primary amines of unsymmetrical diamines has been developed.

Synthesis of some novel phosphorylated and thiophosphorylated benzimidazoles and benzothiazoles and their evaluation for larvicidal potential to Aedes albopictus and Culex quinquefasciatus.

Series of benzimidazole and benzothiazole linked phosphoramidates and phosphoramidothioates (5a-j) and benzimidazole linked phenylphosphoramidates and phenylphosphoramidothioates (10a-e) were synthesized. The title compounds were preliminary screened for mosquito larvicidal properties against Aedes albopictus and Culex quinquefasciatus at different concentration from 40 to 5 mg/L. Among the screened compounds three compounds revealed potential larvicidal effects with 100% mortality in the order of 10e>5j>5e. Compound 10e was found to be the most toxic compound to Ae. albopictus and Cx. quinquefasciatus. The LC50 of 10e against Ae. albopictus was found to be 6.42 and 5.25 mg/L at 24 and 48 h, respectively, whereas it was 7.01 and 3.88 mg/L, respectively in Cx. quinquefasciatus. Temephos was used as positive control.

Trichloroisocyanuric Acid–KF as an Efficient Reagent for One-Pot Synthesis of Dialkylfluorophosphates from Dialkylphosphites

Abstract Trichloroisocyanuric acid–KF afforded dialkylfluorophosphates from dialkylphosphites at room temperature through a facile electrophilic–nucleophilic metathesis.

A DBU–diheteroaryl halide adduct as the fastest current N-diheteroarylating agent

An unexpected diazabicyclo[5.4.0]undec-7-ene (DBU) catalysed rate enhancement of N-arylation of amines with diheteroaryl halides is reported. DBU is found to activate the Ar–Cl bond of a diheteroaryl halide, forming a green coloured adduct under neat conditions. The activated green coloured adduct was used for the arylation of amines under neat conditions and was found to be the fastest diheteroarylating agent reported to date.