An Efficient Method for the Synthesis of 5-Arylisoxazoles from Benzyl Cobaloximes Using Microwave Irradiation

A new and rapid method is described for the synthesis of 5-arylisoxazoles from benzyl cobaloximes using microwave irradiation.     

Solvent-free, ruthenium-catalyzed, regioselective ring-opening of epoxides, an efficient route to various 3-alkylated indoles

Ruthenium-catalyzed regioselective ring-opening of aliphatic and aryl epoxides under solvent-free conditions is reported. It was found that RuCl₃·nH₂O catalyzes the Friedel-Crafts alkylation of indoles, providing 3-alkylated derivatives in good yields under mild reaction conditions.     

The effect of synthesis method and post-synthesis treatment on the formation of neutral Mn(II) complex into anionic zeolite structure and investigation of its catalytic activity in the epoxidation of alkenes

In this study, we improved the catalytic performance of manganese porphyrin encapsulated HY zeolite for alkene epoxidation reaction. For this purpose, Manganese tetra pyridyl porphyrin encapsulated into modified dealuminated Y zeolite (MnTPP-MDAZY) was synthesized using zeolite template synthesis method. This heterogenized catalyst was characterized by FT-IR, UV–Vis, XRD and atomic absorption spectra (AAS) technique. Catalyst loading was 0.263 mmol/g support. In this way, high catalyst loading is probably related to the decrease of the size of metalloporphyrin and the post-synthesis treatment. The latter one causes the increase of the diameter of the mesoporous structure as a result of the dealumination of zeolite with EDTA treatment. High catalyst loading efficiently enhances the epoxidation of alkenes.     

Evaluating the Synthesis of Bis‐pyrazolines

The bis‐cyclization of chalcone with thiosemicarbazide under basic condition led to the formation of new compounds, thiocarbamoyl bis‐pyrazoline derivatives. Bis‐chalcones were prepared by a Claisen–Schmidt condensation between 1 mol bis‐aldehyde and 2 mol acetophenone derivatives in the presence of sodium hydroxide as a catalyst. The structures of all compounds were elucidated by IR, ¹H NMR, and ¹³C NMR spectral data and by elemental analyses.     

One-Pot Synthesis of Novel 2-(Thiazol-2-yl)-4,5-dihydropyridazin-3(2H)-one Derivatives Catalyzed by Activated KSF

A series of 2-(thiazol-2-yl)-4,5-dihydropyridazin-3(2H)-one derivatives were synthesized by one-pot multicomponent cyclocondensation of ketoacid, thiosemicarbazide, and phenacyl bromide using catalytical amount of KSF in EtOH under reflux. The straightforward synthesis, presence of two important class of heterocyclic rings in the individual molecule, easy workup of the products, rapid reaction, mild conditions, and good to excellent yields are notable features of this protocol.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Click activated protodrugs against cancer increase the therapeutic potential of chemotherapy through local capture and activation

A desired goal of targeted cancer treatments is to achieve high tumor specificity with minimal side effects. Despite recent advances, this remains difficult to achieve in practice as most approaches rely on biomarkers or physiological differences between malignant and healthy tissue, and thus benefit only a subset of patients in need of treatment. To address this unmet need, we introduced a Click Activated Protodrugs Against Cancer (CAPAC) platform that enables targeted activation of drugs at a specific site in the body, i.e., a tumor. In contrast to antibodies (mAbs, ADCs) and other targeted approaches, the mechanism of action is based on in vivo click chemistry, and is thus independent of tumor biomarker expression or factors such as enzymatic activity, pH, or oxygen levels. The CAPAC platform consists of a tetrazine-modified sodium hyaluronate-based biopolymer injected at a tumor site, followed by one or more doses of a trans-cyclooctene (TCO)-modified cytotoxic protodrug with attenuated activity administered systemically. The protodrug is captured locally by the biopolymer through an inverse electron-demand Diels–Alder reaction between tetrazine and TCO, followed by conversion to the active drug directly at the tumor site, thereby overcoming the systemic limitations of conventional chemotherapy or the need for specific biomarkers of traditional targeted therapies. Here, TCO-modified protodrugs of four prominent cytotoxics (doxorubicin, paclitaxel, etoposide and gemcitabine) are used, highlighting the modularity of the CAPAC platform. In vitro evaluation of cytotoxicity, solubility, stability and activation rendered the protodrug of doxorubicin, SQP33, as the most promising candidate for in vivo studies. In mice, the maximum tolerated dose (MTD) of SQP33 in combination with locally injected tetrazine-modified biopolymer (SQL70) was determined to be 19.1-times the MTD of conventional doxorubicin. Pharmacokinetics studies in rats show that a single injection of SQL70 efficiently captures multiple SQP33 protodrug doses given cumulatively at 10.8-times the MTD of conventional doxorubicin with greatly reduced systemic toxicity. Finally, combined treatment with SQL70 and SQP33 (together called SQ3370) showed antitumor activity in a syngeneic tumor model in mice.

The Click Activated Protodrugs Against Cancer (CAPAC) platform uses click chemistry to activate cytotoxic drugs directly at a target site with minimal toxicity, overcoming limitations of conventional chemotherapy and traditional targeted therapies.     

Synthesis of chiral 5-aryltetrahydrofuran-2-ones via yeast bioreduction of γ-keto acids and their esters

Enantioselective reduction of γ-keto acids and related γ-keto esters with Saccharomyces cerevisiae (baker’s yeast) leads to the formation of the corresponding chiral 5-aryltetrahydrofuran-2-ones in satisfactory chemical and optical yields. Published in Zhurnal Organicheskoi Khimii, 2006, Vol. 42, No. 3, pp. 379–382. The text was submitted by the authors in English.     

Chemoselective synthesis of δ-lactones via benzyl radical cyclization utilizing K2S2O8-CuCl2

Direct chemoselective oxidation of 8-lactones via highly stable benzyl radical cyclization is reported. The one-pot conversion of premade substituted 5-aryl pentanoic acid and 8-benzyl-1-naphthoic acid in the presence of K2S2O8--CuCl2 results to the δ-lactones in moderate to good yields. The advantages of this methodology is using water as a solvent and utilizing available starting materials.     

Nonlinear-forced vibrations of piezoelectrically actuated viscoelastic cantilevers

This paper aims to study the nonlinear-forced vibrations of a viscoelastic cantilever with a piecewise piezoelectric actuator layer on its top surface using the method of Multiple Scales. The governing equation of motion is a second-order nonlinear ordinary differential equation with quadratic and cubic nonlinearities which appear in stiffness, inertia, and damping terms. The nonlinear terms are due to the piezoelectricity, viscoelasticity, and geometry of the system. Forced vibrations of the system are investigated in the cases of primary resonance and non-resonance hard excitation including subharmonic and superharmonic resonances. Analytical expressions for frequency responses are derived, and the effects of different parameters including damping coefficient, thickness to width ratio of the beam, length and position of the piezoelectric layer, density of the beam, and the piezoelectric coefficient on the frequency-response curves are discussed for each case. It is shown that in all these cases, the response of the system follows a softening behavior due to the existence of the piezoelectric layer. The piezoelectric layer provides an effective tool for active control of vibration. In addition, the effect of the viscoelasticity of the beam on passive control of amplitude of vibration is illustrated.