Synthesis of Privileged Scaffolds by Using Diversity‐Oriented Synthesis

An elegant reagent‐controlled strategy has been developed for the generation of a diverse range of biologically active scaffolds from a chiral bicyclic lactam. Reduction of the chiral lactam with LAH or alkylation with LHMDS to trigger different cyclization reactions have been shown to generate privileged scaffolds, such as pyrrolidines, indolines, and cyclotryptamines. Their amenability to substitution allows us to create various compound libraries by using these scaffolds. In silico studies were used to estimate the drug‐like properties of these compounds. Selected compounds were subjected to anticancer screening by using three different cell lines. In addition, all these compounds were subjected to antibacterial screening to gauge the spectrum of biological activity that was conferred by our DOS methodology. Gratifyingly, with no additional iterative cycles, our method directly generated anticancer compounds with potency at low nanomolar concentrations, as represented by spiroindoline 14 .     

Thiamine hydrochloride as a promoter for the efficient and green synthesis of 12-aryl-8,9,10,12 tetrahydrobenzoxanthene-11-one derivatives in aqueous micellar medium

An environmentally benign, three-component, one-pot integrated chemical process has been developed for the synthesis of 12-aryl-8,9,10,12-tetrahydrobenzoxanthene-11-one by nucleophilic addition reaction between aldehyde and β-naphthol followed by Michael addition of dimedone, catalyzed by thiamine hydrochloride in aqueous micellar medium with excellent yield. Simple reaction conditions, no requirement of chromatographic separation, short reaction time, ease of isolation, use of inexpensive, easily recoverable and reusable catalyst makes this protocol very interesting from an economic and environmental perspective.     

Inclusion complex of Isatoic anhydride with β-cyclodextrin and supramolecular one-pot synthesis of 2, 3-dihydroquinazolin-4(1H)-ones in aqueous media

The inclusion complex of isatoic anhydride with β-cyclodextrin was formed as a result of intermolecular interaction between isatoic anhydride with β-CD. The inclusion complex was confirmed by IR spectroscopy, X-ray diffraction and DSC studies. From application of complex, herein we have described a simple and efficient protocol for synthesis of 2, 3-dihydroquinazoline-4(1H)-one derivatives by one pot condensation of isatoic anhydride, ammonium acetate or amine and aldehyde using β-CD as a supramolecular catalyst in aqueous media.     

An efficient synthesis of furano analogs of duocarmycin C1 and C2: seco-iso-cyclopropylfurano[e]indoline-trimethoxyindole and seco-cyclopropylfurano[f]quinoline-trimethoxyindole

seco-Iso-cyclopropylfurano[e]indoline-trimethoxyindole 1 and seco-cyclopropylfurano[f]quinoline-trimethoxyindole 2 are potent cytotoxic agents. Previous synthesis of these compounds was inefficient and the approach required separation of a mixture containing the isomeric indoline and quinoline intermediates 11 and 12, formed from radical cyclization of allylic bromide 10. Reported herein is an efficient and selective synthesis of either intermediate 11 or 12, thus product 1 or 2, as needed. The conditions of the Stobbe condensation, bromination, 5-exo-trig radical cyclization, amine-carboxylic acid coupling, and debenzylation were optimized for multi gram scale. As a result, the reaction times were shortened, the products were readily isolated, and the yields and purity improved.     

Inhibition of Quorum Sensing,Motility and Biofilm Formation of Pseudomonas aeruginosa by Copper Oxide Nanostructures

Quorum sensing (QS) is the communication between bacterial cells governed by their population density and regulated by the genes controlling virulence factors and biofilm formation. Multiple mechanisms of biofilms are resistive to antimicrobial chemotherapy; therefore novel strategies are required to overcome its limitations. Here, we report the effect of various copper oxide nanostructures (CuO-NSs) on quorum sensing inhibition. The two-dimensional CuO-NSs such as interlaced nanodiscs, nanodiscs and leaf-shaped nanosheets are prepared via a simple chemical method. The Quorum sensing inhibition (QSI) activity of all the CuO-NS are examined using reporter strain Chromobacterium violaceum CV026 and Escherichia coli pSB1142. We found that the CuO-interlaced nanodisc structures exhibit better QSI activity than nanodiscs and leaf-shaped sheets. The interlaced nanodisc structures are inhibited various long-chain N-acyl homoserine lactones (AHLs) mediated QS individually and confirmed by other QS-associated phenomena for Pseudomonas aeruginosa, including biofilm inhibition, inhibition of virulence factors such as pyocyanin, protease production and swarming motility. Thus QSI activity of CuO-NSs is solely dependent on specific shape offering large surface area and more active sites. The CuO-NS is effective quorum sensing inhibitors, which has potential clinical applications in the management of P. aeruginosa associated infections.

     

Synthesis and biological evaluation of novel 4-(6-substituted quinolin-4-yl)-N-aryl thiazol-2-amine derivatives as potential antimicrobial agents

Cyclocondensation reaction of 4-(2-bromoacetyl)quinolin-1-ium bromide ( 4a–d ) with substituted arylthiourea, ( 5a–g ) afforded 4-(6-substituted quinolin-4-yl)-N-aryl/pyridyl thiazol-2-amine ( 6a-ab ). These newly synthesized derivatives were evaluated for in vitro antibacterial activity against Escherichia coli (NCIM 2574), Proteus mirabilis (NCIM 2388) (Gram-negative strains), Bacillus subtilis (NCIM 2063), Staphylococcus albus (NCIM 2178) (Gram-positive strains) and in vitro antifungal activity against Aspergillus niger (ATCC 504) and Candida albicans (NCIM 3100). Compounds 6a , 6b , 6d , 6f , 6k , and 6l showed moderate to good antibacterial activity against S. albus. Ten derivatives 6c , 6q , 6r , 6s , 6t , 6v , 6w , 6x , 6y , and 6aa , showed moderate to good activity against A. niger. N-[4-(Quinolin-4-yl)-1,3-thiazol-2-yl]pyridin-2-amine presented comparable activity against A. niger with respect to standard drug Rouconazole.     

An Isolated Nitridyl Radical‐Bridged {Rh(N.)Rh} Complex

Photochemical activation of [(PNNH)Rh(N₃)] (PNNH=6‐di‐(tert‐butyl)phosphinomethyl‐2,2′‐bipyridine) complex 2 produced the paramagnetic (S=1/2), [(PNN)Rh?N^.‐Rh(PNN)] complex 3 (PNN^?=methylene‐deprotonated PNNH), which could be crystallographically characterized. Spectroscopic investigation of 3 indicates a predominant nitridyl radical (^.N^2?) character, which was confirmed computationally. Complex 3 reacts selectively with CO, producing two equivalents of [(PNN)Rh^I(CO)] complex 4 , presumably by nitridyl radical N,N‐coupling.     

An efficient protocol for the synthesis of 2-amino-4,6-diphenylpyridine-3-carbonitrile using ionic liquid ethylammonium nitrate

Chalcones on condensation with malononitrile and ammonium acetate in the presence of ionic liquid ethylammonium nitrate affords the corresponding 2-amino-4, 6-diphenylpyridine-3-carbonitrile in excellent yield. The ionic liquid is recycled and reused several times.