Synthesis of Diquinolineno[1,3,7,9]Tetraazacyclododecine-7, 15 (14H, 16H)-Dibenzene,and DNA Binding Studies of Macrocyclic Co(II), Cu(II) Complexes: As New Class of Antimicrobial Agent

The synthesis of macrocyclic ligand, diquinolineno[1,3,7,9]tetraazacyclododecine-7, 15 (14H, 16H)-dibenzene(L), is described. The metal complexes of the type [MLX₂], where (M = Co(II) (1), Cu(II) (2) and X = (Cl), have been synthesized by the reaction of ligand(L) with the corresponding metal salts, and characterized by elemental analysis, FT-IR, ¹H-NMR and electronic spectra. The binding property of the complexes with CT-DNA was studied by absorption spectra, viscosity measurements, as well as thermal denaturation studies. The absorption spectral results indicate that the complexes (1) and (2) are binds with base pairs of DNA. The intrinsic binding constant K_b had the value 3.8 × 10⁴M ^?1 for (1 Chappell, L. L., Voss, A. D. and Morrow, J. R. 1998. Inorg. Chem., 37(16): 3989–3998.  [Google Scholar]) and 3.3 × 10⁴ M^?1 for (2), respectively, in 5 mM Tris-HCl/50 mM NaCl buffer at pH 7.2. The viscosity measurement results show the viscosity of sonicated rod-like DNA fragments increased when the complex were added to the solution of calf thymus-DNA. The synthesized ligand and its metal complexes have been screened for antibacterial and antifungal activities.     

QSAR models of cytochrome P450 enzyme 1A2 inhibitors using CoMFA,CoMSIA and HQSAR

Quantitative structure–activity relationship (QSAR) studies were conducted on an in-house database of cytochrome P450 enzyme 1A2 inhibitors using the comparative molecular field analysis (CoMFA), comparative molecular similarity analysis (CoMSIA) and hologram QSAR (HQSAR) approaches. The database consisted of 36 active molecules featuring varied core structures. The model based on the naphthalene substructure alignment incorporating 19 molecules yielded the best model with a CoMFA cross validation value q² of 0.667 and a Pearson correlation coefficient r² of 0.976; a CoMSIA q² value of 0.616 and r² value of 0.985; and a HQSAR q² value of 0.652 and r² value of 0.917. A second model incorporating 34 molecules aligned using the benzene substructure yielded an acceptable CoMFA model with q² value of 0.5 and r² value of 0.991. Depending on the core structure of the molecule under consideration, new CYP1A2 inhibitors will be designed based on the results from these models.     

Accelerating rate calorimeter studies of water-induced thermal hazards of fireworks tip mixture

The objective of this article is to generate thermal decomposition data on fireworks tip mixture, a mixture used to coat the tip of fireworks, for easy ignition. This mixture has reportedly involved in triggering many accidents in fireworks industry. Different quantities of water were added to the mixture and its thermal characteristics were studied. Differential scanning calorimeter was used for screening tests and accelerating rate calorimeter was used for detailed studies in adiabatic and isothermal modes. The self-heat rate data obtained showed onset temperature for different quantity of water, at a range of 80–170 °C. The mixture with 40 % water wt/wt had onset at 80 °C in adiabatic mode. The same mixture on isoaging at 40 °C exhibited exothermic characteristics with a substantial rise in system pressure (57 bar). The heats of exothermic decomposition and Arrhenius kinetics were also computed.     

Synthesis and Self‐Assembly of Bolaamphiphiles Based on β‐Amino Acids or an Alcohol

The synthesis of bolaamphiphiles from unusual β‐amino acids or an alcohol and C₁₂ or C₂₀ spacers is described. Unusual β‐amino acids such as a sugar amino acid, an AZT‐derived amino acid, a norbornene amino acid, and an AZT‐derived amino alcohol were coupled with spacers under standard conditions to get the novel bolaamphiphiles 5 – 8 (Scheme 1), 12 and 13 (Scheme 2), and 17 and 20 (Scheme 3). Some of these compounds, on precipitation from MeOH/H₂O, self‐assembled into organized molecular structures.     

Synthesis of Novel Fluorinated 11H‐Azaindolo[3,2‐c]isoquinolines

A series of novel fluorinated 11H‐azaindolo[3,2‐c]isoquinolines ( 7 ) have been synthesized starting from 2(1H)pyridones ( 1 ) via azaindoles ( 5 ). Initially, compound 1 was treated with POCl₃/DMF, and the resulting compound 2 was reacted with benzylamine to obtain compounds 3 that were subjected to cyclization after protecting the secondary amine to get azaindoles ( 5 ). Further, compounds 5 were subjected to cyclization as per Pictet–Spengler reaction condition. However, it was not successful. Subsequently, the azaindoles ( 5 ) were acetylated and then cyclized to give title compounds 7 . These compounds are new and well characterized by spectral data.     

Zinc-Mediated Facile and Efficient Chemoselective S-Alkylation of 5-Aryl-1,3,4-oxadiazole-2-thiols in the Absence of Base

Zinc-mediated facile and efficient chemoselective S-alkylation of 5-aryl 1,3,4-oxadiazole-2-thiols in the presence of a catalytic amount of tetra butyl ammonium iodide was described. The reaction was performed under neutral conditions. The chemoselectivity of the alkylation was confirmed by NMR spectroscopy and x-ray crystallography.     

Rapid Access for the Synthesis of 1‐N‐Methyl‐spiro[2.3′]oxindole‐spiro[3.7″] (3″‐Aryl)‐5″‐methyl‐3″,3a″,4″,5″,6″,7″‐hexahydro‐2H‐pyrazolo[4,3‐c]pyridine‐4‐aryl‐pyrrolidines Through Sequential 1,3‐Dipolar Cycloaddition and Annulation

The 1,3‐dipolar cycloaddition of an azomethine ylide, generated from isatin and sarcosine by a decarboxylative route with various p‐substituted 3,5 bis(aryl methylidene)N‐methyl‐4‐piperidinones in refluxing methanol, proceeded regioselectively to give novel dispiroheterocycles. The product on subsequent annulation with hydrazine hydrate afforded 1‐N‐methyl‐spiro[2.3′]oxindole‐spiro[3.7″](3″‐aryl)‐5″‐methyl‐3″,3a″,4″,5″,6″,7″‐hexahydro‐2H‐pyrazolo[4,3‐c]pyridine‐4‐aryl‐pyrrolidines in good yield.     

BF3·OEt2-catalyzed synthesis of 1-(tetrahydropyran-3-yl)-1,3-dihydroisobenzofuran and trans-fused hexahydropyrano[3,2-c]chromene derivatives

A novel intramolecular Prins cyclization of (E)-5-(2-(hydroxymethyl)phenyl)pent-4-en-1-ol with aldehydes has been achieved using 10 mol % BF₃·Et₂O to produce 1-(tetrahydropyran-3-yl)-1,3-dihydroisobenzofuran derivatives in good to excellent yields with high selectivity. Similar type of coupling with salicylaldehydes provides the trans-fused hexahydropyrano[3,2-c]chromene derivatives in excellent yields.     

p-Tolyl isocyanate derivatization for analysis of CWC-related polar degradation products by mass spectrometry

Most of the precursors and/or degradation products related to the Chemical Weapons Convention (CWC) are polar. Identification of these molecules in environmental samples provides clues regarding the alleged usage and/or synthesis of the parent toxic chemicals. Such polar compounds need to be derivatized in order to analyze them by gas chromatography–mass spectrometry (GC–MS). In this study, we developed a new derivatizing reagent, para-tolyl isocyanate (PTI), for derivatization of polar CWC-related compounds. The PTI reagent selectively derivatizes the –OH and/or?SH functional groups with high efficiency, but does not react with carboxylic acid (?COOH) or phosphonic acid (?(O)P(OH)₂) groups. The PTI derivatives of dialkyl aminoethanols, dialkyl aminoethanol-N-oxides, and 3-quinuclidinol were successfully eluted through GC, and their electron ionization (EI) mass spectra were distinct and provided the structure information by which the isomeric compounds can be easily distinguished. We also calculated the GC-retention index values that can be used for further confirmation of the target compounds. All the studied PTI derivatives can be analyzed by EI-MS with direct insertion probe and/or by direct electrospray ionization mass spectrometry (ESI-MS) together with the MS–MS data; both sets of data provide full structure information. The PTI reagent was found to be better in some respects than the conventional bistrimethylsilyl trifluoroacetamide (BSTFA), a trimethyl silylating reagent. The PTI reagent is commercially available, and the PTI derivatives are highly stable for months and are not sensitive to moisture. The applicability of the PTI derivatization for trace-level determination of the target CWC-related polar compounds in environmental matrices and in human plasma samples is also evaluated.

Synthesis and Structural Proof of a Potent 5-Lipoxygenase Inhibitor

Abstract  

5-Lipoxygenase inhibitor 3-O-acetyl-9,11-dehydro-β-boswellic acid was detected in the extract of Boswellia serrata gum resulting from unstable 11-hydroxy precursor. It was reported more potent than other Boswellic acids in its inhibition of 5-Lipoxygenase. Here, we report the method of conversion of 3-acetoxy-β-boswellic acid to 3-O-acetyl-9,11-dehydro-β-boswellic acid, and the crystal structure of later. This compound crystallizes in orthorhombic space group P2₁2₁2₁ with cell parameters of a = 12.726(1) ?, b = 16.597(1) ?, c = 27.332(2) ?, α = β = γ = 90°, V = 5772.7(5) ?³, D _c = 1.143 Mg/m³, and Z = 8. The X-ray structure investigation indicates that the rings A, B, D and E are exhibit chair and the ring C adopts a distorted half chair conformation. The conformational difference of the two structures in the arrangement is due to crystal packing of 3-O-acetyl-9,11-dehydro-β-boswellic acid. The molecular packing is stabilized by C–H···O and O–H···O types of hydrogen bonding interactions.