Separation, characterization, and quantitation of process-related substances of the anti-hypertensive drug doxazosin mesylate by reversed-phase LC with PDA and ESI-MS as detectors

A simple and rapid reversed-phase liquid chromatography (LC) method with photodiode array (PDA) and electrospray ionization (ESI)-mass spectrometry (MS) as detectors was developed and validated to separate, identify, and quantitate the related substances of Doxazosin mesylate (DXZN) for monitoring the reactions involved during process development. The high-performance liquid chromatography profiles of related-substances of DXZN are used as fingerprints to follow the procedures used in the manufacturing units. The separation is accomplished on an Inertsil ODS-3 column with acetonitrile-ammonium acetate (10 mM, pH 4.0) as the mobile phase, using a gradient elution mode and monitoring the eluents by a photodiode array detector at 265 nm at ambient temperature. LC-ESI-MS-MS is used to identify the additional impurities formed during the synthesis. The identified impurities were synthesized and characterized by UV, Fourier transform-IR, 1H NMR, and MS data. The detection limits for the impurities are 0.74 - 4.14 x 10(-9) g, and the method is found to be suitable not only for the monitoring of synthetic reactions, but also for quality assurance of DXZN in bulk drugs and formulations.     

Total Synthesis of Kopsinitarine E

Kopsinitarines A–E are complex octacyclic caged Kopsia alkaloids with strained cage skeletons and a unique cyclic hemiaminal bridge that makes total synthesis challenging. Herein, we disclose the first total synthesis of kopsinitarine E. The key synthetic features include a SmI₂-mediated radical cascade cyclization and a subsequent semi-pinacol rearrangement to install the key carbocyclic skeleton, a chemoselective hydrosilyl amide reduction to construct the hemiaminal ether bridge, and an intramolecular Mannich reaction to establish the highly strained cage system.     

Trace elements in the scalp hair of patients with alcohol induced psychosis

A number of essential trace elements play a major role in various metabolic pathways and in many diseases like autoimmune, neurological and psychiatric. This study is undertaken with an aim to evaluate the levels of different trace elements in the scalp hair samples of patients suffering from alcohol induced psychosis by particle induced X-ray emission technique (PIXE). It is observed that Fe (p?<?0.0005), Cu (p?<?0.001) are significantly higher in the hair samples of alcohol induced psychosis patients compared to those in normals while concentrations of Mn (p?<?0.005) and Zn (p?<?0.0001) are lower. The concentrations of Co and Ni in the hair samples are found to be in consonance with the concentrations in the normals.     

Late-Stage Chemoenzymatic Installation of Hydroxy-Bearing Allyl Moiety on the Indole Ring of Tryptophan-Containing Peptides

The late-stage functionalization of indole- and tryptophan-containing compounds with reactive moieties facilitates downstream diversification and leads to changes in their biological properties. Here, the synthesis of two hydroxy-bearing allyl pyrophosphates is described. A chemoenzymatic method is demonstrated which uses a promiscuous indole prenyltransferase enzyme to install a dual reactive hydroxy-bearing allyl moiety directly on the indole ring of tryptophan-containing peptides. This is the first report of late-stage indole modifications with this reactive group.     

The facile and efficient organocatalytic platform for accessing 1,2,4-selenadiazoles and thiadiazoles under aerobic conditions

The first organocatalytic approach towards synthesis of rarely explored 1,2,4-selenadiazole and thiadiazole scaffolds have been devised using corresponding carboxamides as substrates. The transformations were realized using two distinct conditions in the presence of catalytic vitamin B₃ or thiourea under aerobic conditions. Developed methods overcome the associated limitations of previous reported approaches and the desired products were obtained in high yields and selectivity without the formation of toxic side-products.     

Regioselective synthesis of 2-carbonyl furans in a one pot three component reaction

Regioselective synthesis of 2-benzoyl-6,6-dimethyl-6,7-dihydrobenzofuran-4(5H)-ones have been accomplished through a novel protocol involving β-amino enone, N-chlorosuccinimide and dimedone in a one pot catalyst-free reaction at an ambient temperature. On the other hand, the same reaction when conducted with two equivalents of N-chlorosuccinimide under similar reaction conditions, exclusive formation of 2-benzoyl-3-(dimethylamino)-6,6-dimethyl-6,7-dihydrobenzofuran-4(5H)-ones were observed. Simple and metal-free reaction conditions, selective product formation and excellent yields are the advantages of this protocol.     

A divergent approach for the synthesis of some polyhydroxy pyrrolidines and piperidines from ribosylamine

A simple and efficient synthesis of 1,4-dideoxy-1,4-imino-d-ribitol, 1,4-dideoxy-1,4-imino-l-lyxitol, N-benzyl derivative of d-ribitol, 3,4,5-trihydroxy-piperidine, l-4-epi-isofagomine and d-3-epi-isofagomine, which are glycosidase inhibitors has been described from the commercially available d-ribose as a starting material.     

One‐Pot Three‐Component Domino Reaction for the Synthesis of Novel Spiro Indolinyl Isoxazolo[2,3‐c][1,3,5]Thiadiazepinones Catalyzed by PTSA

The synthesis of novel spiro indolinyl isoxazolo[2,3‐c] [1,3,5]thiadiazepinones has been achieved by using one‐pot three‐component domino reaction from 3‐amino‐5‐methylisoxazole, substituted isatins, and mercapto acetic acid by employing p‐toluene sulfonic acid as Lewis acid catalyst. The salient features of the present method are mild reaction conditions, cost effective, environmentally benign, high yields of products and operational simplicity.     

Catalyst-free synthesis of pyrazole-aniline linked coumarin derivatives and their antimicrobial evaluation

Catalyst-free one-pot CN and CC bond formation is described as a simple and ecofriendly method for the synthesis of pyrazole-aniline linked coumarin derivatives. Employing this protocol, a series of derivatives were synthesized in good to excellent yields and tested against different bacterial strains as well as fungal strains. Most of the compounds exhibited potential antimicrobial activity against both Gram-positive and Gram-negative bacterial strains. Among them, the compounds 4b, 4e, 4?h, 4i and 4?k exhibited promising activity on all the tested bacterial strains with values ranging between 1.9 and 7.8?µg/mL. In addition, these compounds were tested against various fungal strains and were found to exhibit potential antifungal activity. Fascinatingly, among the tested derivatives, the compounds 4e, 4?h and 4i were found to be equipotent to miconazole (positive control) against some of the tested fungal strains. Moreover, these compounds showed promising bactericidal, Candida-cidal and biofilm inhibition activities. Further, mechanistic study was carried out with the most active derivative 4i indicated that these compounds inhibit the ergosterol biosynthesis pathway.     

具有精准结构Zr-O及Zr/Ti-O纳米团簇的深共熔溶剂热合成

近年来,深共熔溶剂热作为一种绿色合成方法被广泛用于多种杂化功能材料的合成。在本研究中,这一合成方法被引入到多核Zr-和Zr/Ti-O纳米团簇的制备,成功获得被邻菲罗啉、苯酚等共轭配体修饰的Zr₆以及Ti₁₁Zr₄团簇。此方法将为具有精准结构信息的被较多发色团包覆的纳米团簇的合成开辟新的技术路线。此外,光催化分解水产氢实验结果表明,由于具有不同的簇核环境,这两种纳米团簇表现出不同的分散性及与之相关的产氢活性。因此,该研究也为探索金属氧簇材料的结构–性能关系以及结构设计原则提供了借鉴。