Diversity oriented approach to crownophanes by enyne metathesis and Diels-Alder reaction as key steps

Various crownophanes are assembled starting with simple phenol derivatives such as catechol, resorcinol, and hydroquinone. Here, cross-enyne metathesis (CEM) and Diels-Alder (DA) reaction have been used as key steps. This strategy has embedded six diversity points.     

Synthesis of benzyl halide derivatives of spirohydantoins via [2+2+2] cyclotrimerization reaction

Generally, synthesis of hydantoin derivatives involve use of carbonyl compounds which in turn require multistep synthesis. Here, we report a new approach to assemble spirohydantoins via [2+2+2] cyclotrimerization reaction using commercially available, inexpensive hydantoin as a starting material.     

Novel Schiff base metal complexes: synthesis,characterization, DNA binding,DNA cleavage and molecular docking studies

A novel Schiff base, 3-(((1H-1,2,4-triazol-3-yl)imino)methyl)-4H-chromen-4-one (L) was synthesized and used as ligand for the synthesis of Co(II), Ni(II), Cu(II), Zn(II) and Pd(II) complexes. The structural characterization of the ligand and its metal complexes was determined by using various physicochemical and spectroscopic methods. The IR data show that the Schiff base ligand acts as a bidentate donor coordinating through the oxygen atom of the chromone and nitrogen atom of the imine group. Based on all spectral data, tetrahedral geometry has been proposed for all the metal complexes except Cu(II) and Pd(II) complexes. However, square-planar geometry has been proposed for Cu(II) and Pd(II) complexes. DNA binding interaction of the ligand and its metal complexes was investigated by using UV–visible absorption, fluorescence and molecular docking studies. The binding constants were in the order of 10⁴ M^?1 suggesting good binding affinity towards CT-DNA. The DNA cleavage activity of the synthesized compounds was investigated by using agarose gel electrophoresis. In vitro antimicrobial activity of the synthesized compounds were screened against two gram-positive bacteria (Bacillus subtilis, Staphylococcus aureu) and two gram-negative bacteria (Escherichia coli, Proteus vulgaris) and one fungi strain Candida albicans using disc diffusion method. Antioxidant activity was carried out by DPPH radical scavenging method. In vitro anti-proliferative activity of the ligand and its metal complexes was also carried on the HEK-293, HeLa, IMR-32 and MCF-7 cancer cell lines using MTT assay.     

Synthesis of 1,3-cis-Fused Tricyclic System through Regio- and Stereoselective Epoxidation and Ring-Rearrangement Metathesis: Access To Basic Core of Presilphiperfolanols

Here, we report a new synthetic approach to a highly strained 1,3-fused cis-cis-cis-5/5/6 tricyclic system that appeared among the presilphiperfolanol analogues. The cis-fusion of six-membered ring to a diquinane moiety is accomplished by substrate-controlled regio- and stereoselective epoxidation, and ring-rearrangement metathesis (RRM) sequence. In this regard, both early-, and late-stage epoxidation and RRM reactions were studied. The target compound, cis-cis-cis-5/5/6 tricyclic ketone with an α,β-oxirane ring can serve as a key building block to produce various presilphiperfolanol analogues. The cis-cis-cis-5/5/6-tricyclic-α,β-epoxyketone can also act as masked enone and therefore useful for various chemical transformations in organic synthesis. The short synthetic sequence disclosed here may be useful to design various biologically important molecules. The newly reported molecules are well-characterized by NMR, HRMS, and IR spectral data.     

Late-stage Modification of Cage Diones by Tandem Metathesis

Herein, we report the application of tandem ring-opening cross-metathesis (ROCM) and tandem ring-opening cross-metathesis followed by cross-metathesis (ROCM/CM) in highly strained diastereomeric heptacyclic cage diones (HCCD's) catalyzed by ruthenium catalysts. These caged diastereomeric compounds have a high degree of ring strain as well as steric congestion. Therefore, the present work related to ROCM is unique and intricate as compared to simple norbornene derivatives. It is useful to prepare new hexacyclic cage derivatives suitable for high-energy density materials. The synthetic strategy of starting cage compounds features the Diels-Alder reaction, and [2+2] photocycloaddition as key steps.     

Synthesis,Characterization and Luminescence Sensitivity with Variance in pH,DNA and BSA Binding Studies of Ru(II) Polypyridyl Complexes

Three ruthenium(II) polypyridyl complexes, [Ru(phen)₂(mip)](ClO₄)₂ (1) (phen =1,10-Phenanthroline), [Ru(bpy)₂(mip)](ClO₄)₂ (2) (bpy = 2,2’bipyridyl) and [Ru(dmb)₂(mip)](ClO₄)₂ (3) (dmb = 4, 4′-dimethyl 2, 2′-bipyridine), were synthesized with an intercalative ligand mip (2-morpholino-1H-imidazo[4,5-f][1, 10]phenanthroline) and characterized by ¹H, ¹³C–NMR, IR, UV-vis, mass spectra and elemental analysis. pH effect, ion selectivity (cations, anions) and solvent sensitivity of complexes were studied. The interaction of these complexes with DNA was performed using absorption, emission spectroscopy and viscosity measurements. The experimental results indicated that the two complexes interacted with calf thymus DNA (CT-DNA) by intercalative mode. BSA (Bovine Serum Albumin) protein binding of these complexes was studied by UV-visible and fluorescence techniques. The binding capacity of these complexes was explained theoretically by molecular docking method.     

Palladium(II) complexes of 5-substituted isatin thiosemicarbazones: Synthesis,spectroscopic characterization,biological evaluation and in silico docking studies

Substituted heterocyclic (isatin) appended thiosemicarbazone ligands (L1–L3) are synthesized by condensation of substituted isatin molecule with N(4)-phenyl-3-thiosemicarbazide in good yields. The palladium(II) complexes are synthesized from ligands (L1–L3) and PdCl₂, with a general formula [PdCl(X-C₁₅H₁₀N₄OS)] where X?=?5-chloro (1), 5-bromo (2), and 5-nitro (3). Both analytical and spectroscopic methods have been used for the analysis and characterization of the synthesized compounds. The antimicrobial activity results observed that complexes, 1 and 2 have registered potent antibacterial activity against B. subtilis and K. pneumoniae and also complex 2 has shown good antifungal activity against the micro organisms. The antioxidant activity analysis revealed that the complex 3 showed significant activity with IC₅₀ values 7.24?±?0.09?µM. Moreover, the in vitro antiproliferative activity results suggested that complex 3 exhibited high activity against HeLa cell line compared with the standard with the IC₅₀ value 16.52?±?1.08?µM. The docking results correlate well.     

Application of ring-rearrangement metathesis in organic synthesis: A grand design

In this report, we compiled various strategies involving a ring-rearrangement metathesis as a key step to assemble diverse molecules. Popular name reactions such as Grignard reaction, Overman rearrangement, Fischer indolization, Beckmann rearrangement and Diels–Alder reaction were used in combination with ring-rearrangement metathesis to construct complex targets. Additionally, CH activation and RRM strategy has been used to assemble azacycles. In some instances, the ring-rearrangement metathesis was expected to occur; however, ring-opening metathesis products were realized. These methods were included in the miscellaneous section. We anticipate that the lessons learned here are useful in designing complex polycyclic and heterocyclic targets suitable for biological and material science applications. Beside our work, we have also included others work as a background information.     

One-pot synthesis of carbazoles from indoles via a metal free benzannulation

We report a simple, one-pot, and metal free benzannulation protocol to carbazoles starting with indoles, carbonyl compounds and an appropriate dienophiles. Mechanistically, this strategy generates an in situ diene by condensation between indole and carbonyl compound succeed and subsequent dehydration. Later, Diels–Alder reaction of this diene with a suitable dienophile followed by oxidation delivers the carbazole derivative. This methodology provide an easy access to carbazoles containing 1,4-naphthoquinone moiety.     

Synthesis,Structural, Biological Evaluation,Molecular Docking and DFT Studies of Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) Complexes bearing Heterocyclic Thiosemicarbazone ligand

A new ligand, 2‐aminonicotinaldehyde N‐methyl thiosemicarbazone (ANMTSC) and its metal complexes [Co(II) ( 1 ); Ni(II) ( 2 ); Cu(II) ( 3 ); Zn(II) ( 4 ); Cd(II) ( 5 ) or Hg(II) ( 6 )] were synthesized. The compounds were characterized by analytical methods and various spectroscopic (infrared, magnetic, thermal, ¹H, ¹³C NMR, electronic and ESR) tools. The structure of ANMTSC ligand was confirmed by single crystal X‐ray diffraction study. The spectral data of metal complexes indicate that the ligand acts as mononegative, bidentate coordination through imine nitrogen (N) and thiocarbonyl sulphur (S^?) atoms. The proposed geometries for complexes were octahedral ( 1 – 2 ), distorted octahedral ( 3 ) and tetrahedral ( 4 – 6 ). Computational details of theoretical calculations (DFT) of complexes have been discussed. The compounds were subjected to antimicrobial, antioxidant, antidiabetic, anticancer, ROS, studies and EGFR targeting molecular docking analysis. Complex 5 has shown excellent antibacterial activity and the complexes 2 and 5 have shown good antifungal activity. The complexes 1 and 4 displayed good antioxidant property with IC₅₀ values of 11.17 ± 1.92 μM and 10.79 ± 1.85 μM, respectively compared to standard. In addition, in vitro anticancer activity of the compounds was investigated against HeLa, MCF‐7, A549, IMR‐32 and HEK 293 cell lines. Among all the compounds, complex 4 was more effective against HeLa (IC₅₀ = 10.28 ± 0.69 μM), MCF‐7 (IC₅₀ = 9.80 ± 0.83 μM), A549 (IC₅₀ = 11.08 ± 0.57 μM) and IMR‐32 (10.41 ± 0.60 μM) exhibited superior anticancer activity [IC₅₀ = 9.80 ± 0.83 ( 4 ) and 9.91 ± 0.37 μM ( 1 )] against MCF‐7 compared with other complexes.