Interaction between bovine serum albumin (BSA) and phosphorus heterocycles (PHs) was studied using multi-spectroscopic techniques. The results indicated the high binding affinity of PHs to BSA as it quenches the intrinsic fluorescence of BSA. The experimental data suggested the fluorescence quenching mechanism between PHs and BSA as a dynamic quenching. From the UV–vis studies, the apparent association constant (Kapp) was found to be 9.25×102, 1.27×104 and 9.01×102 L/mol for the interaction of BSA with PH-1, PH-2 and PH-3 respectively. According to the Förster's non-radiation energy transfer (FRET) theory, the binding distances between BSA and PHs were calculated. The binding distances (r) of PH-1, PH-2 and PH-3 were found to be 2.86, 3.03, and 5.12 nm, respectively, indicating energy transfer occurs between BSA and PHs. The binding constants of the PHs obtained from the fluorescence quenching data were found to be decreased with increase of temperature. The negative values of the thermodynamic parameters ΔH, ΔS and ΔG at different temperatures revealed that the binding process is spontaneous; hydrogen bonds and van der Waals interaction were the main force to stabilize the complex. The microenvironment of the protein-binding site was studied by synchronous fluorescence and circular dichroism (CD) techniques and data indicated that the conformation of BSA changed in the presence of PHs. Finally, we studied the BSA-PHs docking using Autodock and results suggest that PHs is located in the cleft between the domains of BSA.

No abstract

A facile synthesis of [1,2,3]triazolo dibenzo[1,5]diazocines by intramolecular Huisgen 1,3-dipolar cycloaddition of azide with alkynes has been achieved. The methodology offers clean reaction and easy isolation of products in excellent yields.

3H-pyrano[3,2-f]quinoline-3-one, 4-methyl-4,7-phenanthrolin-3(4H)-one, and 1,3-dimethylpyrido[3,2-d]pyrimidine-2,4(1H,3H)-dione derivatives have been synthesized by hitherto unreported silver-catalyzed 6-endo-dig mode of cycloisomerization from various N-propargylated heterocyclic compounds. The silvercatalyzed reaction provides the synthesis of potential bioactive compounds in excellent yields.There is flurry of activities on the synthesis of quinoline and its annulated derivatives due to their broad spectrum of biological profiles, which includes antialergic, antidiabetic, antimicrobial, analgesic, insecticidal, antifungal, antipyretic, tyrosine kinase inhibition, and also cytotoxic properties. 1 Due to these bioactivities quinoline derivatives are widely used in pharmaceutical and agrochemical sectors, besides these derivatives are also used as functional materials. 2 The quinoline derivatives have gained considerable attention due to their central role as building blocks in the synthesis of natural products. 3 On the other hand natural products possessing coumarin, quinolone, and uracil subunits show wide range of bioactivity. 4 There are many alkaloids which contain pyrido-coumarin, pyrido-quinolone skeleton, due to the presence of these cores the alkaloids are also bioactive. 5 Some examples of natural products are dutadrupine, helietidine, geibalansine, and amphimedine. 6 Moreover bioactivity of pyrido-pyrimidines are well known, 7 besides their antibacterial and antiallergic properties they also inhibit enzyme adenosine kinase (AK) and dihydrofolate reductase (DHFR). 8 Recently, it has been found that substituted pyridines efficiently inhibit HMG-CoA reductase and cholesterol transport proteins. 9Traditional approaches 10 have frequently been employed for the synthesis of quinoline ring system in the total synthesis of quinoline based alkaloids. However, all these reactions usually require harsh conditions, tedious reaction procedure, or give poor yield. Over the last two decades, there has been growing interest for the development of syntheses of quinoline derivatives, which include radical reaction, 11 iodine-mediated cyclization, 12 and metal-catalyzed reaction. 13 Nevertheless, these are improvements over traditional methods. However, these methods also have some limitations. Some methods are not environmentally benign in terms of toxicity, 11,12 some are time consuming processes or having different byproducts. 13 A thorough search of literature reveals that there are a few examples of activated gold-and copper-catalyzed cycloisomerization reactions to afford substituted pyridine and quinoline derivatives. 14 To our knowledge, there is no such report for the synthesis of bioactive pyridocoumarin or pyridoquinolone or pyridopyrimidine solely by silvercatalyzed reaction. This prompted us to undertake a study to develop a methodology for the synthesis of these heterocycles. We report here the results of our investigation.The required precursors 3a-f were prepared in high yields by the reaction of 1a-c w...

SummaryReaction of o-azidobenzenesulfonamides with ethyl carbonochloridate afforded the corresponding amide derivatives, which gave 3-ethoxy-1,2,4-benzothiadiazine 1,1-dioxides through an intramolecular aza-Wittig reaction. The reaction was found to be general through the synthesis of a number of benzothiadiazine 1,1-dioxides. Acid-catalyzed hydrolysis of 3-ethoxy-1,2,4-benzothiadiazine 1,1-dioxides furnished the 2-substituted benzothiadiazine-3-one 1,1-dioxides in good yields and high purity, which is the core moiety of RSV inhibitors.

A new efficient approach for the synthesis of unsymmetricaly substituted piperazine 2,5-dione derivatives is described by using intramolecular aza-Wittig reaction as the key step. The reaction conditions are very simple, offer easy isolation, and excellent yields of the products.2,5-Diketopiperazines, known as cyclic dipeptides, are frequently formed from both enzymatic and nonenzymatic processes of peptides/protein. 1 They are also wellknown as byproducts that are formed during removal of temporal protecting group of secondary amino acids. 2 The piperazine-2,5-dione moiety occurs in a variety of drugs and natural products which show interesting biological activities 3 including antiviral, 4 antifungal, 5 antitumour, 6 antithrombic, 7 and antibacterial activities. 8 Additionally this heterocyclic system has found unique applications as an acceptor for organic anions or metal cations 9 and in material science. 10 While numerous approaches have been reported 11-14 for the synthesis of piperazine 2,5-diones there is still demand for more easier synthetic pathways. Generally, synthesis of 2,5-DKP starting from amino acids or amino esters requires protection, deprotection, and cyclization reactions which occur either in situ or at elevated temperatures.The aza-Wittig reaction has become one of the most important synthetic method for the construction of C=N, N=N, and S=N double bonds especially in the preparation of nitrogen containing heterocycles. Iminophosphoranes, nitrogen analogues of phosphorus ylides, are versatile intermediates in modern synthetic chemistry. 15 Numerous research papers and reviews have appeared in the literature describing the general use of iminophosphorane as reagent and intermediate in organic synthesis, 16 including the synthesis of heterocyclic natural products by the azaWittig method. 17In continuation of our research interest in the synthesis of nitrogen heterocycles 18 we have undertaken a study to synthesize 2,5-diketopiperazine derivatives of biological interest from N-substituted amino esters using intramolecular aza-Wittig reaction as the key step, and the results are reported here.The precursors 3a-f required for our present study were synthesized from the amino esters 1a-f. Treatment of 1a-f with chloroacetyl chloride under phase-transfer-catalysis conditions gave the amides 2a-f. The amide formation reaction under the PTC conditions proceeded at a much faster rate than any normal amide formation reaction.Compound 2a-f were then treated with excess of sodium azide in DMF solution at 90°C to afford the azide compounds 3a-f in good to excellent yields (Scheme 1).Scheme 1 Reagents and conditions: (i) chloroacetyl chloride, CH 2 Cl 2 -H 2 O, K 2 CO 3 , r.t.; (ii) NaN 3 , DMF, 90°C.Initially, the intramolecular aza-Wittig reaction was conducted with the substrate 3a. When 3a was treated with triphenylphosphine in THF at room temperature, product 6a was afforded along with triphenylphosphine oxide. The intermediate iminophosphorane 4 was not isolated (Scheme 2). Scheme 2 Reagents and co...

No abstract

A catalyst-free, one-pot strategy for the synthesis of 1,2,3-triazole-fused 1,4-benzodiazepinone derivatives from N-substituted 2-azidobenzamides and propargyl bromide, in the presence of a base, is reported. The products are formed in good to excellent yields via N-alkylation followed by a 1,3-dipolar cycloaddition.