Synthesis and Pharmacological Evaluation of a Novel Series of 2‐((2‐Aryl thiazol‐4‐yl)methyl)‐5‐(alkyl/alkylnitrile thio)‐1,3,4‐oxadiazole Derivatives as Possible Antifungal Agents

In the present investigation, a novel series of 2‐[(2‐arylthiazol‐4‐yl)methyl]‐5‐(alkyl/alkylnitrile thio)‐1,3,4‐oxadiazole derivatives were synthesized by cyclo‐condensation of 2‐(2‐substituted thiazol‐4‐yl)aceto hydrazide with carbon disulfide followed by S‐alkylation with alkyl halide in dry acetone. All the newly synthesized compounds were characterized by spectral (IR, ¹H NMR, ¹³C NMR, mass, and elemental analysis) methods. The title compounds were screened for in vitro antifungal activity and most of the synthesized compounds show moderate to good antifungal activity.     

One-step method for synthesis of 2,4-disubstituted quinazoline 3-oxides by reaction of a 2-aminoaryl ketone with a hydroxamic acid using Zn(OTf)2 as the catalyst

A simple and efficient method for the preparation of 2,4-disubstituted quinazoline 3-oxides by reaction of a hydroxamic acid with 2-aminoaryl ketones using zinc(II) triflate as the catalyst is described.     

Synthesis of fused thiazolo[3,2-a]pyrimidinones: N-aryl-2-chloroacetamides as doubly electrophilic building blocks

2-Chloro-N-phenylacetamide and N-(benzo[d]thiazol-2-yl)-2-chloroacetamide are doubly electrophilic building blocks for the formation of ring annulated thiazolo[3,2-a]pyrimidinone products. This synthetic route involves formation of the title compound in acceptable product yields by the elimination of the by-product, aniline/2-aminobenzothiazole. Analytical and spectral studies, as well as single crystal X-ray data on the representative compound 6c confirmed the structure of all the reaction products.     

Aminol initiated Prins cyclization for the synthesis of octahydro-1H-pyrano [3,4-c]pyridine and hexahydro-1H-furo[3,4-c]pyrrole derivatives

Various aldehydes undergo smooth coupling with a branched homoallylic alcohol appended N-tosyl amine (1 & 3) in the presence of 10 mol % BF₃·OEt₂ at room temperature to afford a novel class of 1,8-disubstituted octahydropyrano[3,4-c]pyridine and 1,6-disubstituted hexahydrofuro[3,4-c]pyrrole derivatives in good yields, respectively.     

Total synthesis of catenioblin B

Herein we report the first total synthesis of catenioblin B (1) via a titanium(IV) mediated regioselective epoxide ring-opening, Grignard reaction, Luche’s reduction and TEMPO/BAIB mediated intramolecular cyclization as the key steps.     

Selective separation and characterization of the stress degradation products of ondansetron hydrochloride by liquid chromatography with quadrupole time‐of‐flight mass spectrometry

Ondansetron hydrochloride was subjected to forced degradation studies under various conditions of hydrolysis (acidic, basic, and neutral), oxidation, photolysis, and thermal as prescribed by International Conference on Harmonisation guideline Q1A (R2). A simple, selective, precise, and accurate high‐performance liquid chromatography method was developed on a Waters Xterra C₁₈ (150 × 4.6 mm id, 3.5 μm) column using 10 mM ammonium formate (pH 3.0)/methanol as a mobile phase in gradient elution mode at a flow rate of 0.6 mL/min. The method was extended to liquid chromatography quadrupole time‐of‐flight tandem mass spectrometry for identification and structural characterization of stress degradation products of ondansetron. The drug showed significant degradation in base hydrolytic and photolytic stress conditions in the liquid state, while it was found to be stable in neutral, acidic, thermal, and oxidative stress conditions. A total of five degradation products were characterized and most probable mechanisms for the formation of degradation products have been proposed on the basis of a comparison of the fragmentation of the [M + H]⁺ ions of the drug and its degradation products. Finally, the developed method was validated in terms of specificity, linearity, accuracy, precision, and robustness as per International Conference on Harmonisation guideline Q2 (R1).     

Structural consequences of weak interactions in dispirooxindole derivatives

Spiro scaffolds are being increasingly utilized in drug discovery due to their inherent three‐dimensionality and structural variations, resulting in new synthetic routes to introduce spiro building blocks into more pharmaceutically active molecules. Multicomponent cascade reactions, involving the in situ generation of carbonyl ylides from α‐diazocarbonyl compounds and aldehydes, and 1,3‐dipolar cycloadditon with 3‐arylideneoxindoles gave a novel class of dispirooxindole derivatives, namely 1,1′′‐dibenzyl‐5′‐(4‐chlorophenyl)‐4′‐phenyl‐4′,5′‐dihydrodispiro[indoline‐3,2′‐furan‐3′,3′′‐indoline]‐2,2′′‐dione, C₄₄H₃₃ClN₂O₃, (I), 1′′‐acetyl‐1‐benzyl‐5′‐(4‐chlorophenyl)‐4′‐phenyl‐4′,5′‐dihydrodispiro[indoline‐3,2′‐furan‐3′,3′′‐indoline]‐2,2′′‐dione, C₃₉H₂₉ClN₂O₄, (II), 1′′‐acetyl‐1‐benzyl‐4′,5′‐diphenyl‐4′,5′‐dihydrodispiro[indoline‐3,2′‐furan‐3′,3′′‐indoline]‐2,2′′‐dione, C₃₉H₃₀N₂O₄, (III), and 1′′‐acetyl‐1‐benzyl‐4′,5′‐diphenyl‐4′,5′‐dihydrodispiro[indoline‐3,2′‐furan‐3′,3′′‐indoline]‐2,2′′‐dione acetonitrile hemisolvate, C₃₉H₃₀N₂O₄·0.5C₂H₃N, (IV). All four compounds exist as racemic mixtures of the SSSR and RRRS stereoisomers. In these structures, the two H atoms of the dihydrofuran ring and the two substituted oxindole rings are in a trans orientation, facilitating intramolecular C—H...O and π–π interactions. These weak interactions play a prominent role in the structural stability and aid the highly regio‐ and diastereoselective synthesis. In each of the four structures, the molecular assembly in the crystal is also governed by weak noncovalent interactions. Compound (IV) is the solvated analogue of (III) and the two compounds show similar structural features.     

Characterization of N,N‐dimethyl amino acids by electrospray ionization–tandem mass spectrometry

Methylation is an essential metabolic process for a number of critical reactions in the body. Methyl groups are involved in the healthy function of the body life processes, by conducting methylation process involving specific enzymes. In these processes, various amino acids are methylated, and the occurrence of methylated amino acids in nature is diverse. Nowadays, mass‐spectrometric‐based identification of small molecules as biomarkers for diseases is a growing research. Although all dimethyl amino acids are metabolically important molecules, mass spectral data are available only for a few of them in the literature. In this study, we report synthesis and characterization of all dimethyl amino acids, by electrospray ionization–tandem mass spectrometry (MS/MS) experiments on protonated molecules. The MS/MS spectra of all the studied dimethyl amino acids showed preliminary loss of H₂O + CO to form corresponding immonium ions. The other product ions in the spectra are highly characteristic of the methyl groups on the nitrogen and side chain of the amino acids. The amino acids, which are isomeric and isobaric with the studied dimethyl amino acids, gave distinctive MS/MS spectra. The study also included MS/MS analysis of immonium ions of dimethyl amino acids that provide information on side chain structure, and it is further tested to determine the N‐terminal amino acid of the peptides. Copyright © 2015 John Wiley & Sons, Ltd.     

Palladium‐Catalyzed Regio‐ and Stereoselective Cross‐Addition of Terminal Alkynes to Ynol Ethers and Synthesis of 1,4‐Enyn‐3‐ones

Conjugated enynes, enol ethers, and enynones are versatile building blocks that can be elaborated by a wide variety of synthetic transformations. The selective synthesis of such units is a prerequisite for their effective utilization. The synthesis of conjugated 2‐phenoxyenynes through a palladium‐catalyzed cross‐addition of terminal alkynes to phenylethynyl ethers (hydroalkynylation) is now presented. The reaction is highly regio‐, stereo‐, and chemoselective, and shows excellent tolerance toward functional groups. The addition further features very mild reaction conditions (room temperature) and an inexpensive catalytic system (without a ligand and with a cheaply available Pd catalyst). The thus synthesized enynyl ethers with allylic hydroxy tethers, which survived the reaction, were shown to be ready precursors for valuable 1‐en‐4‐yn‐3‐ones.     

Metal‐Free Decarboxylative Cyclization/Ring Expansion: Construction of Five‐, Six‐, and Seven‐Membered Heterocycles from 2‐Alkynyl Benzaldehydes and Cyclic Amino Acids

A one pot synthesis of 1H‐benzo[g]indoles, tetrahydrobenzo[h]quinolines, and naphtho[1,2‐b]azepines from 2‐alkynyl benzaldehydes and cyclic amino acids is reported. The salient feature of the strategy involves formation of three new bonds (one C? N and two C? C bonds) by a metal‐free decarboxylation/cyclization/one‐carbon ring expansion sequence in one pot.