Synthetic Communications最新文献

A simple and efficient route for the synthesis of a series of new mono/bis isoxazolines, and pyrroline linked chromone heterocyclic hybrids has been developed from 2-aminochromone via key intermediate mono and 2-(diallylamino)chromen-4-one. The intermediate subjected to the [1,3] dipolar cycloaddition with insitu generated nitrile oxides and ring-closing metathesis to generate the regio selective Isoxazolines and 3-pyrrolines. All the derivatives were screened for their anti-cancer activity (Cell viability), compared to the standard drug Imatinib. Compounds 13b and 13e, 14b and 14g showed good inhibition at 10 µM concentration.

Breast cancer and lung cancer causes a high rate of mortality all over the world. Pursuing our efforts toward searching for efficient anticancer agents herein a series of coumarin/piperazine hybrids 10a-f, 12a-d, 14 were synthesized and subsequently assessed for their potential In Vitro anticancer activity, against A549 (Lung cancer) and MCF-7 (breast cancer) cell lines using MTT assay. Encouragingly, all the synthesized compounds displayed varying degrees of effectiveness, ranging from good to moderate activity against these two cancer cell lines. However, amongst all the compounds synthesized, compound 12c exhibited notably higher potency against both A549 and MCF-7 cell lines, with an IC₅₀ of 0.40 µM and 0.51 µM, respectively. Additionally, the study delved deeper by conducting EtBr/AO assays, unveiling the induction of apoptosis. Furthermore, investigations into Reactive Oxygen Species (ROS) were conducted by using DCFH-DA dye. To understand the behavioral patterns and selectivity of the synthesized compounds, computational techniques were employed alongside experimental analysis. Utilizing density functional theory (DFT) calculations, electronic and structural characteristics were determined for compound 12c These calculations were then compared and associated with the observed biological effects. Additionally, molecular docking was utilized to investigate how compounds 12c interacted with crucial apoptotic genes, specifically targeting p53 and caspase 3. Compound 12c exhibited docking scores of −8.4 kcal/mol and −7.9 kcal/mol for p53 and caspase 3 respectively. Lastly, an in Silico ADME study was performed to evaluate the compounds’ potential as drug candidates.

Recently, photoredox catalysis using 9,10-phenanthrenequinone (PQ) has emerged as an efficient method for the transformation of various organic compounds. Low cost and good availability make it a promising alternate to typical transition metal complex-based photocatalysts. It has emerged as an alternative in photoredox catalysis highlighting recent advancement in organic transformation using (PQ) as photocatalyst.

A new method for the synthesis of 2-(phenyl)indole via the cyclization of 2-(phenylethynyl)aniline in the presence of K₂S was established, which was used to prepare 2-(phenyl)indole derivatives in high yields (66%-93%). Mechanistic studies have revealed that a trisulfur radical anion (S₃^•−) is generated from K₂S, which acts as an initiator for the intramolecular addition of the alkyne and the amino group in o-alkynylaniline, ultimately leading to the formation of the indole derivative. This method provides a new way to prepare 2-(phenyl)indoles and a novel application of S₃^•− in organic synthesis.

Reduction of styrene compounds was achieved by the simple method of adding more than 2.5 equivalents of an aqueous HI solution in chlorobenzene under refluxing conditions for 8 h to give the product in medium to excellent yields. There was no need to add further additional reagent and catalyst. HI was a specific reagent for this reduction reaction. Increment of the amount of HI was efficient to increase the yield rather than to elongate the reaction time. This reaction could be applied to compounds bearing halogen and sulfur atoms, which would act as reductive site and poisoning of the transition-metal catalyst, respectively. The yield was decreased in the case of the compounds bearing small substituent such as propyl and butyl groups on olefin. This reaction proceeded via the iodinated intermediate followed by the reduction of C-I bond. The reduction mechanism would contain the radical cleavage of the C-I bond.

Novel library of pyrazole derivatives (6a–k) from substituted 4-dioxaborolanyl-1H-pyrazole and halo benzaldehyde through simultaneous Suzuki reaction, nucleophilic addition, and hydrolysis under moderate reaction conditions. The desired compounds 6a–k have been formed in good to high yield. All the compound structures were characterized by analytical and spectral (¹H NMR,¹³C NMR and MS) studies. Furthermore, the evaluation of biological activity of synthesized molecules.

An efficient method for the synthesis of indolo[2,1-a]isoquinolines using calcium carbide as an alkyne source, 2-(2-bromophenyl)-1H-indoles as starting materials, and copper as a catalyst is described. The target products are synthesized via Sonogashira cross-coupling/nucleophilic addition tandem reactions. The advantages of this protocol include the use of inexpensive and easy-to-handle solid alkyne source instead of flammable and explosive gaseous acetylene, cheap and readily available raw materials, wide range of substrates, and simple reaction procedure. The method can also be extended to gram scale. In addition, the desired product can also be obtained by one-pot three-component reaction of phenylhydrazine hydrochlorides, o-bromoacetophenones and calcium carbide.

A series of quinoline-thiazole appended 1,4-disubstituted 1,2,3-triazole were synthesized by performing Cu(I) catalyzed 1,3-dipolar cycloaddition reaction (“Click” reaction) and fully characterized by various spectral techniques like FTIR, NMR and HRMS. These compounds were evaluated for in vitro antimalarial activity against plasmodium falciparum. All the compounds (7a–7y) exhibited moderate to good activity in comparison to standard drug Quinine. Compound 7r (IC₅₀ 0.19 µg/mL) displayed appreciable activity comparable to Quinine (IC₅₀ 0.268 µg/mL). Further antimicrobial screening of the synthesized substituted triazoles were also carried out against two gram (+) bacteria (Staphylococcus aureus, Bacillus subtilis), two gram (–) bacteria (Escherichia coli, Klebsiella pneumonia) and two fungi (Candida albicans, Aspergillus niger). Results revealed that compound 7r reflected promising antimicrobial activity among the synthesized library of molecules. Molecular docking studies of broadly active antimalarial disubstituted triazoles 7m and 7r were explored in the active site of enzyme dihydroorotate dehydrogenase (DHODH) to have the probable mode of action.

The one-pot reaction of potassium cyanocarbamimidothiolates with acetylated bromo sugars produced a novel class of substituted glycosylisothiourea derivatives 5a–h that demonstrated their Z-configuration. Some of the later compounds 5a–d were treated with NH₃ in methanol at 25 °C, to afford the unprotected thioglycoside functionalized compounds 6a–c with excellent yields. To characterize the structure of the newly synthesized compounds, various techniques, such as elemental analysis and spectral data (¹³C NMR, IR, and ¹H NMR) were employed. Furthermore, the substituted S-glycosylisothioureas 5 and 6 were subjected to a reaction with hydrazine hydrate, resulting in the formation of corresponding 5-amino-1,2,4-triazole derivatives 7a–d. The antibacterial properties of all newly synthesized compounds were thoroughly assessed and evaluated. Among these compounds, the most potent antimicrobial agents were found to be compounds 5a, 5g, 6a, 6b, and 6c.

Choline hydroxide (ChOH) is an effective ionic liquid (IL) that enables the straightforward construction of β-phosphonomalonates in basic medium. A variety of compounds, including aromatic/heterocyclic and aliphatic aldehydes (1a–p) were reacted with dicyanomethane (2) and diethyl phosphonate (3) to produce the targeted products in good yields (4a–p). The constructed compounds as well as the IL were characterized using spectral ¹H, ¹³C, and ³¹P NMR.