Synthesis of Polycyclic γ-Lactams by Ni(0)-Catalyzed [2+2+1] Cycloaddition of Imines and
3-[2-(5-Aryl-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4-yl]-4hydroxy-6-methyl-2H-pyran-2-ones 6a-h were synthesized via the ring closure reactions of 3-phenyl-5-aryl-4,5-dihydropyrazole-1-carbothioamides 3a-h with 3-(bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one 5.The new synthesized thiazolyl-pyrazolinyl-pyran-2-one compounds were evaluated for their potential antioxidant activity by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical method.The molecular docking of the synthesized compounds on DPPH oxidase protein showed a high binding affinity, confirming the experimental results recorded.The synthesized compounds deserve a consideration for further analyses regarding the control of oxidative stress and their use as possible antioxidant agents in the pharmaceutical industry.
From the peels of Citrus sphaerocarpa, two new limonoids, sphaerocarpain Ⅰ and Ⅱ were isolated together with five known compounds including methyl deacetylnomilinate and ichangin.The chemical structures of the new compounds were elucidated based on chemical/physicochemical evidence.For sphaerocarpain Ⅰ and Ⅱ, the absolute configuration was established by comparison of experimental and predicted electronic circular dichroism (ECD) data.Among the isolated compounds, sphaerocarpain I, II, methyl deacetylnomilinate and ichangin showed cytotoxic activity against both human neuroblastoma cells (SH-SY5Y) and human glioblastoma cells (U-251 MG).
– Antioxidants play an essential role in preventing oxidative stress. In this study, we synthesized novel tocopherol analogs with heterocyclic rings such as quinoline ( 5 ), indole ( 6 ), and benzimidazole ( 7 ), and evaluated their radical scavenging activities. The results showed that 6 has excellent radical scavenging activity. The data suggested that radical scavenging activity was enhanced in compounds containing heterocyclic rings with sufficient π-electrons and decreased in compounds with heterocyclic rings deficient π-electrons.
The recently synthesized 1-chloro-11-oxo-3,4-dihydro-11H-chromeno[4,3-b]quinoline-2-carboxaldehyde (1) was efficiently utilized as a key precursor to construct a diversity of polyfused systems containing chromeno[4,3-b]quinoline. Reaction of compound 1 with some substituted hydrazines afforded pyrazoles annulated chromeno[4,3-b]quinoline. Treatment of compound 1 with a diversity of 1,3-N,N-binucleophiles led to pyrimidines annulated chromeno[4,3-b]quinoline. In addition, a diversity of fused pyridines annulated chromeno[4,3-b]quinoline were synthesized from condensation of compound 1 with a variety of 1,3-C,N-binucleophiles. Finally, the reactivity of compound 1 was tested towards a diversity of 1,4-binucleophilic reagents. Structures of the new compounds were established using spectral and analytical data.
– Maleimide-fused aceheptylenes were prepared using guaizulene as a starting material. The condensation reaction of 3,4-diformylguaiazulene derivative, which was prepared in three steps from guaiazulene, with maleimides in the presence of tri-n -butylphosphine and 1,8-diazabicyclo[5.4.0]undec-7-ene afforded the maleimide-fused aceheptylenes. Structural feature of the aceheptylenes prepared was revealed by 1 H NMR spectroscopy and nucleus-independent chemical shift calculations.
The chemistry of 3-(2-oxo-2H-chromen-3(6)(8)-yl)-1-aryl/heteroaryl-1H-pyrazole-4-carbaldehydes has gained increased interest in both synthetic organic and biological fields, since a large number of developments in the use of such compounds seem to be of considerable value.This review describes all the available synthetic methods for diverse 3-(2-oxo-2H-chromen-3(6)(8)-yl)-1-aryl/ heteroaryl-1H-pyrazole-4-carbaldehydes in the literature survey.It also summarizes thier chemical behaviors as building blocks towards a variety of chemical reagents to construct related compounds as well as their biological applications.
A range of naturally occurring indoloquinolines, such as neocryptolepine and isocryptolepine, have been found to possess antimicrobial and anticancer activity.To broaden our understanding of this class of compound´s biological capacity we herein report the results of a screening campaign of a total of 9 11H-indolo[3,2-c]quinolines, 19 neocryptolepine analogues, and two isocryptolepine analogues towards a panel of both Gram-positive (Enterococcus faecialis, Staphylococcus aureus, and Streptococcus agalactiae) and Gramnegative (Escherichia coli and Pseudomonas aeruginosa) bacteria.The compounds were also tested for their cytotoxicity against human liver cells (HepG2) and human fetal lung fibroblast (MRC-5).Several of the compounds showed antimicrobial and cytotoxic activity, making them interesting for further optimization as antimicrobial or anticancer agents.The indoloquinolines neocryptolepine (1) and isocryptolepine (2) (Figure 1) belongs to a class of tetracyclic N-heterocycles that are commonly found in natural products, 1 agrochemicals, 2 and drug candidates. 3Due to the vast range of biological activity possessed by this group of compounds there has been a great interest in developing synthetic strategies for their preparation. 1,4The broad variety of pharmacological properties found in this group of compounds therefore warrants further exploration. 1,5Particular interesting is the activity some derivatives possess against methicillin-resistant Staphylococcus aureus (MRSA), a bacterial infection that is hampered by increasing antibiotic resistance, unresponsive to many broad-spectrum βlactam antibiotics, 6 and drug-resistant biofilms, which are rapidly becoming a global health threat. 7
A series of uridine-based compounds homologated at C-4' with an aryl-substituted oxazole ring were prepared.Conversion of 2',3'-O-cyclopentylidene uridine to the corresponding 4'-carboxylate followed by Steglich ester coupling with a series of azidoalcohols gave the corresponding azidoesters.The azidoesters were cyclized to the substituted oxazolines using Staudinger aza-Wittig conditions (PPh3/THF).Direct treatment of the substituted oxazolines with nickel peroxide or DDQ provided the corresponding C4' uridyl aryloxazoles.Removal of the 2',3'-O-cyclopentylidene group was accomplished using 70% aqueous trifluoroacetic acid which afforded the target C4'-heterocyclic nucleoside analogues.The sequence could be accomplished with nitrogen or oxygen-substituted aryl azidoalcohol precursors which gave rise to the corresponding aryl-substituted C4'-oxazolyl uridine derivatives.The oxygen or nitrogen-substituted aryloxazoles underwent further derivatization to deliver ester and amide derivatives.
Fluorinated heterocycles are a major component of the field of modern medicinal chemistry due to the widespread presence of heterocyclic ring structures in naturally occurring biological molecules.The effect of the presence of fluorinated heterocyclic moieties on chemical properties such as intermolecular interactions and solubility can be used to impart synthetic molecules with useful, drug-like characteristics.Pyridazines, which are aromatic six-membered rings with a chemical formula (CH)4N2 and adjacent nitrogens, afford important biological activities to drug molecules by increasing their solubility and ability to complex with target molecules.Our method of synthesizing fluorinated pyridazines incorporates an SNAr reaction on 5,6-fused ring pyridazines with a variety of aryl substituents at the 1-and 4-positions with pentafluoropyridine.The target products were identified by spectroscopic characterization and confirmed via X-ray crystallography.Computational studies were also performed on the phenylsubstituted case, including the calculation of an optimized structure using PBE with a cc-pVTZ basis.This analysis found the addition of perfluorinated pyridine significantly altered the esp mapping, HOMO-LUMO, and NBOs of the modified pyridazine compared to other 5,6-fused ring heterocycles.
– The aza-Diels-Alder reaction is a [4+2] cycloaddition, involving the insertion of nitrogen atom into dienes or dienophiles. A series of biologically and pharmaceutically active essential heterocycles have been developed as a result of this approach. This method witnessed as a powerful tool for the construction of a diverse range of biological active quinoline scaffolds and other nitrogen containing heterocyclic compounds due to its operational modesty, high atom economy, regio-and stereoselectivity. The present report focuses on the advancement of aza-Diels-Alder reaction for the synthesis of optically active and inactive quinoline derivatives.
Imidazo[1,2-a]pyridine exerts a notable pharmacological efficiency and has emerged as an integral backbone for the treatment of various cancer.Inhibition of cyclin-dependent kinases has emerged as a potential therapeutic strategy for a variety of cancers.Here, we discuss the synthesis of imidazo[1,2-a]pyridine derivatives modified at positions 6 and 8 prepared using Suzuki-Miyaura crosscoupling, Buchwald reaction, and peptide coupling as the main synthetic methods.All synthesized compounds were characterized by spectroscopy techniques after purification and screened for their anti-cancer activity by in vitro MTT assays against MCF-T cell line and CDK2 inhibition by kinase inhibition assay.The in vitro and kinase inhibition assay revealed that compounds 11ii, 11iii, 11xxi, 11vi, and 11viii show potent anti-cancer activity for the treatment of breast cancer.This study demonstrates that substituted imidazo[1,2-a]pyridine can be exploited for future cyclin-dependent kinase (CDK2) inhibitor development.
