Efficient Synthesis and Docking Analysis of Selective CDK9 Inhibitor NVP-2

Graphical AbstractNVP-2 (1), a potent and selective inhibitor of cyclin-dependent kinase 9 (CDK9), showed potent antitumor activity in preclinical studies. In this work, we designed and adopted a convergent synthetic route to efficiently synthesize NVP-2 (1). The key intermediate (7) was synthesized from malononitrile (2) and 1-bromo-2-(2-bromoethoxy)ethane (3) by successive cyclization, reduction, nucleophilic substitution with 2-bromo-6-fluoropyridine, and Suzuki–Miyaura reaction with (5-chloro-2-fluoropyridin-4-yl)boronic acid. Another key intermediate (11) was synthesized from (S)-1-methoxypropan-2-ol (8) by reaction with TsCl, electrophilic substitution reaction with tert-butyl ((1r,4r)-4-aminocyclohexyl)carbamate, and then by deprotection of Boc. Finally, a substitution reaction by the key intermediates (7) and (11) to afford the target product NVP-2 (1). The reaction conditions of the whole synthesis process were simple and mild, free of harsh conditions such as the microwave reaction and dangerous reagents in the original patent, and realized the efficient synthesis of NVP-2. In addition, we analyzed the binding mode of NVP-2 in the active pocket of CDK9 to provide reasonable design ideas for subsequent discovery of novel CDK9 inhibitors.

Lewis Acid Combined with Microwave Converts Hemicellulose and Cellulose in Cane Pith into 5-Hydroxymethylfurfural and Glucose

The paper using sugarcane pith as a raw material, the feasibility of aluminum hydroxide Lewis acid combined with microwave conditions to be used as a resource was investigated.Under the conditions of the combination of stellate acid and microwave, the 5-hydroxymethyl furfural (5-HMF) in 0.9% of the liquid phase product can be detected, and its low yield of 0.9% is worthy of further improvement. Economic analysis shows that the added value of 5-HMF produced by Lewis acid combined with microwave is as high as about 30,000 yuan per ton, and the prospect of resource utilization is huge. Use oxalic acid to hydrolyze the remaining cellulose and hemicellulose after 5-HMF is prepared from sugarcane pith to glucose, which is used in food and related products. It has very important application value in the industry. In this paper, the hemicellulose in cane pith is converted to 5-HMF under microwave reaction conditions, and then the remaining residue of the reaction is hydrolyzed with oxalic acid to produce glucose, which provides theoretical basis and technical support for further research on the high-value utilization of sugar cane pith in the future.

Gelation of uranyl ions and gel-derived uranium oxide nanoparticles for gas sensing

Gas sensing uranium oxide nanoparticles were synthesized by microwave reaction based on uranyl-ethylene-glycol gel.

Microwave-assisted Synthesis of 1-(perfluorohexyl)-3-methylimidazolium iodide

ABSTRACTA perfluorinated ionic liquid, 1-(perfluorohexyl)-3-methylimidazolium iodide, was synthesized via microwave reaction and compared to a non-fluorinated analog. Typically, the synthesis of fluorinated ionic liquids involves long reaction times and multiple steps. We have demonstrated a shortened synthesis and a more straightforward procedure, by using a microwave reactor for the microwave-assisted synthesis of 1-(perfluorohexyl)-3-methylimidazolium iodide. The addition of fluorinated alkyl chains on imidazolium ionic liquid cations increases the molecular free volume of the ionic liquid which is beneficial for increasing CO2 physisorption. Computational and experimental data shows an increased CO2 solubility and capacity for fluorinated ionic liquids. The perfluoroalkyl functionalized ionic liquid is characterized using 1H and 19F NMR spectroscopy, FTIR spectroscopy, and DSC. By DSC, a crystallization onset is near -31 °C and while the onset of the melting point between -30 and -17 °C.

Microwave Assisted Green Synthesis of Benzimidazole Derivatives and Evaluation of Their Anticonvulsant Activity

Background: Benzimidazole is the fused heterocyclic aromatic compound. It is an essential pharmacophore and privileged structure for the development of new drug molecules. These are bioactive molecules present in various anthelmintic drugs such as albendazole, mebendazole, parbendazole, triclabendazole etc. Methods: Benzimidazole derivatives are synthesized by reaction between orthophenylene diamine and anthranillic acid followed by acetylation in the presence of acetic anhydride. Finally, the acetylated products undergo Claisen-Schimdt condensation with various substituted benzaldehydes to produce corresponding benzimidazole derivatives or chalcones. Both conventional and microwave irradiation technology are followed to get the titled compounds. The titled compounds are screened for their anticonvulsant and neurotoxicity activity. Results: By the help of microwave synthesis, the yield of product was increased in less reaction time. So, it follows Green chemistry approach by making above reactions eco-friendly. Some of the compounds exhibited significant anticonvulsant activity as compared to standard drug. Conclusion: In the present investigation, we have synthesized novel benzimdazole derivatives with chalone moiety to improve the biological activity. The compounds were obtained under microwave reaction with high yield in a short reaction time.

Ligand-Related Precursors of Luminescent Carbon Nanofibers Synthesized by Microwave Reaction

Luminescent carbon nanomaterials are important materials for sensing, imaging, and display technologies. This work describes the use of microwave heating for the template-assisted preparation of luminescent carbon nanofibers (CNFs) from the reaction of a range of beverage-related precursors with the nitrogen-rich polyethyleneimine. Highly luminescent robust carbon fibers that were 10 to 30 μm in length and had a diameter of 200 nm were obtained under moderate conditions of temperature (250–260 °C) and a short reaction time (6 min). The high aspect ratio fibers showed wavelength-dependent emission that can be readily imaged using epifluorescence. The development of these multi-emissive one-dimensional (1D) carbon nanomaterials offers potential for a range of applications.

A greener and sustainable approach for converting polyurethane foam rejects into superior polyurethane coatings

Recycling is a crucial area of research in green polymer chemistry. Various developments in recycling are driven by Environmental concerns, interest in sustainability and desire to decrease the dependence on non-renewable petroleum based materials. Polyurethane foams [PUF] are widely used due to their light weight and superior heat insulation as well as good mechanical properties. As per survey carried Polyurethane Foam Association, 12 metric tonnes of polyurethane foam are discharged during manufacturing and/or processing and hence recycling of PUF is necessary for better economics and ecological reasons. In present study, rejects of PUF is subjected to reaction with a diethylene amine in presence of sodium hydroxide [NaOH] as catalyst, as a result depolymerised product containing hydroxyl and amine groups is obtained. Conventional and Microwave reaction for depolymerizing polyurethane foam have been carried, and best results are obtained by Microwave reaction. Further depolymerised product with hydroxyl and amine functionalities are reacted with bis (2-hydroxyethyl terephthalate) [BHET] obtained by recycling polyethylene terephthalate [PET] and sebacic acid, with stannous oxalate [FASCAT 2100 series] as catalyst to obtain Polyester amides. These Polyester amides having hydroxyl and amino groups in excess are cured with isocyanates-hexamethylene diisocyanate biuret [HDI biuret] and isophorone diisocyanate [IPDI] for coating applications. The coated films are characterized using physical, mechanical and chemical tests, which shows comparable physical, mechanical properties but alkali resistance is poor.