Correction and removal of expression of concern: A general and concise asymmetric synthesis of sphingosine, safingol and phytosphingosines via tethered aminohydroxylation.

Correction and removal of expression of concern for 'A general and concise asymmetric synthesis of sphingosine, safingol and phytosphingosines via tethered aminohydroxylation' by Pradeep Kumar, et al., Org. Biomol. Chem., 2010, 8, 5074-5086, DOI: 10.1039/C0OB00117A.

4-Phenyl quinoline derivatives as potential serotonin receptor ligands with antiproliferative activity.

Antagonists of signaling receptors are often effective non-toxic therapeutic agents. Over the years, there have been evidences describing the role of serotonin or 5-hydroxytryptamine (5-HT) in development of cancer. Although there are reports on the antiproliferative effects of some serotonin receptor antagonists, there are very few investigations related to understanding their structure-activity relationships. In this study, we report the screening of a library of 4-phenyl quinoline derivatives for their antiproliferative activities. Preliminary docking studies indicated that these ligands had the ability to bind to two of the serotonin receptors, 5-HT1B and 5-HT2B. The results of the in silico experiments were validated by performing in vitro studies on MCF-7 breast cancer cell line. The ethylpiperazine derivatives showed maximum toxicity against this cancer cell line. The compounds inhibited Calcium ion efflux (induced by serotonin) and ERK activation. One of the most active 4-phenyl quinoline derivatives (H3a) also induced apoptosis, thereby, suggesting the use of this scaffold as a potential anticancer drug.

4'-Epi-DNA: A DNA Mimic Containing 4'-hydroxymethyl-α-l-Xylo-Thymidine with Compact Backbone like RNA.

Synthesis of C4'-epi-DNA containing 3'→ 5″ linkages is reported for the first time. Crystal structure study of the monomer indicated that though the dihedral angle O3'-C3'-C4'-C5″ in this case would be like in RNA, the sugar conformation would remain like that in DNA. The study of the effect of this backbone configuration in DNA with respect to its binding to cDNA and RNA is reported in this note.

New pimarane diterpenes and other antimycobacterial metabolites from Anisochilus verticillatus.

Phytochemical investigation of the acetone extract of the aerial parts of Anisochilus verticillatus afforded a new 8,9-secopimarane diterpene (1), two new isopimarane diterpenes (2, 3) and the known ursolic acid (4), α-amyrin (5), ß-amyrin (6), stigmast-5-en-3-one (7) and hydroxychavicol (8). Structures of the new compounds were elucidated with the help of 1D and 2D nuclear magnetic resonance spectroscopic data, and single crystal X-ray crystallography of compound 3. Compounds 2 and 8 inhibited Mycobacterium tuberculosis H37Ra with an IC50 of 11.3 (IC90 of 20.0 µg/mL) and 12.5 µg/mL, respectively. Correspondingly, molecular docking studies with Extra Precision Glide revealed a correlation between score and biological activity for these compounds to describe the molecular basis for the most significant SAR results.

Conformational modulation of peptides using ß-amino benzenesulfonic acid ((S)Ant).

This communication describes the utility of a conformationally restricted aromatic ß-amino acid (2-aminobenzenesulfonic acid, (S)Ant) inducing various folding interactions in short peptides. Sandwiching (S)Ant between diverse amino acid residues was shown to form robust folded architectures featuring a variety of H-bonded networks, suggesting its utility in inducing peptide folding.

Divergent total synthesis of 1,6,8a-tri-epi-castanospermine and 1-deoxy-6,8a-di-epi-castanospermine from substituted azetidin-2-one (ß-lactam), involving a cascade sequence of reactions as a key step.

A divergent, short, and novel total synthesis of 1,6,8a-tri-epi-castanospermine (7) and 1-deoxy-6,8a-di-epi-castanospermine (8) has been developed via a common precursor, 15, obtained from D-mannitol derived ß-lactam. The key step involves a one pot cascade sequence of trimethyl sulfoxonium ylide based cyclization of epoxy sulfonamide 14via epoxide ring opening, one carbon homologation followed by intramolecular cyclization.

Conformational modulation of peptide secondary structures using ß-aminobenzenesulfonic acid.

This communication describes the influence of ß-aminobenzenesulfonic acid ((S)Ant) on the conformational preferences of hetero foldamers. The designed (Aib-(S)Ant-Aib)n and (Aib-(S)Ant-Pro)n oligomers display a well-defined folded conformation featuring intramolecular mixed hydrogen bonding (7/11) and intra-residual (6/5) H-bonding interactions, respectively.

Monitoring cellular uptake and cytotoxicity of copper(II) complex using a fluorescent anthracene thiosemicarbazone ligand.

The thiosemicarbazone derivative of anthracene (ATSC, anthracene thiosemicarbazone 1) and its copper(II) complex (CuATSC, 2) were synthesized and characterized by spectroscopic, electrochemical, and crystallographic techniques. Interaction of 1 and 2 with calf thymus (CT) DNA was explored using absorption and emission spectral methods, and viscosity measurements reveal a partial-intercalation binding mode. Their protein binding ability was monitored by the quenching of tryptophan emission using bovine serum albumin (BSA) as a model protein. Furthermore, their cellular uptake, in vitro cytotoxicity testing on the HeLa cell line, and flow cytometric analysis were carried out to ascertain the mode of cell death. Cell cycle analysis indicated that 1 and 2 cause cell cycle arrest in sub-G1 phase.

Synthesis, spectroscopic characterization and structural investigations of new adduct compound of carbazole with picric acid: DNA binding and antimicrobial studies.

Carbazole picrate (CP), a new organic compound has been synthesized, characterized by various analytical and spectroscopic technique such as FT-IR, UV-Vis, (1)H and (13)C NMR spectroscopy. An orthorhombic geometry was proposed based on single crystal XRD study. The thermal stability of the crystal was studied by using thermo-gravimetric and differential thermal analyses and found that it was stable up to 170°C. Further, the newly synthesized title compound was tested for its in vitro antibacterial and antifungal activity against various bacterial and fungal species. Also, the compound was tested for its binding activity with Calf thymus (CT) DNA and the results show a considerable interaction between CP and CT-DNA.

Antimycobacterial labdane diterpenes from Leucas stelligera.

Phytochemical investigation of the acetone extract of the aerial parts of Leucas stelligera afforded four new compounds (1-4) belonging to the labdane diterpene series as well as two known flavones, velutin (5) and chrysoeriol (6). Structure elucidation of the new compounds was carried out using 1D and 2D NMR spectroscopic data and single-crystal X-ray crystallography of compound 1. Compounds 1-4 exhibited selective antimycobacterial activity against Mycobacterium tuberculosis with IC50 values in the range 5.02-9.80 µg/mL.

Sugar furanoid trans-vicinal diacid as a γ-turn inducer: synthesis and conformational study.

A simple method for the synthesis of a sugar furanoid trans vicinal diacid and its incorporation into the N-terminal tetrapeptide sequence (H-Phe-Trp-Lys-Thr-OH) to get glycopeptide has been described. 2D NMR and MD simulation studies of clearly show that the sugar diacid adopts a γ-turn conformation towards the N-terminus.

A synthetic zipper peptide motif orchestrated via co-operative interplay of hydrogen bonding, aromatic stacking, and backbone chirality.

Here, we report on a new class of synthetic zipper peptide which assumes its three-dimensional zipper-like structure via a co-operative interplay of hydrogen bonding, aromatic stacking, and backbone chirality. Structural studies carried out in both solid- and solution-state confirmed the zipper-like structural architecture assumed by the synthetic peptide which makes use of unusually remote inter-residual hydrogen-bonding and aromatic stacking interactions to attain its shape. The effect of chirality modulation and the extent of noncovalent forces in the structure stabilization have also been comprehensively explored via single-crystal X-ray diffraction and solution-state NMR studies. The results highlight the utility of noncovalent forces in engineering complex synthetic molecules with intriguing structural architectures.

New dipyranocoumarin from the leaves of Calophyllum apetalum Willd.

A new dipyranocoumarin, α-hydroxytomentolide A (1) was isolated from the leaves of Calophyllum apetalum together with the known compounds friedelin (2), apetalactone (3), inophyllum C (4) and canophyllol (5). The structure of the new compound was established by spectroscopic studies which include (1)H NMR, (13)C NMR, NOESY, HetCOSY, COLOC experiments and single crystal X-ray diffraction analysis.

NHC-catalyzed reaction of enals with hydroxy chalcones: diastereoselective synthesis of functionalized coumarins.

The N-heterocyclic carbene-catalyzed annulation of enals with 2'-hydroxy chalcones afford cyclopentane-fused coumarin derivatives with an excellent level of diastereocontrol. The reaction tolerates a broad range of functional groups; 25 examples are given, and a preliminary mechanistic investigation is provided.

Carboxamide versus sulfonamide in peptide backbone folding: a case study with a hetero foldamer.

Strikingly dissimilar hydrogen-bonding patterns have been observed for two sets of closely similar hetero foldamers containing carboxamide and sulfonamides at regular intervals. Although both foldamers maintain conformational ordering, the hydrogen-bonding pattern and backbone helical handedness differ diametrically.

Design, synthesis, structural characterization by IR, (1) H, (13) C, (15) N, 2D-NMR, X-ray diffraction and evaluation of a new class of phenylaminoacetic acid benzylidene hydrazines as pfENR inhibitors.

Recent studies have revealed that plasmodial enoyl-ACP reductase (pfENR, FabI), one of the crucial enzymes in the plasmodial type II fatty acid synthesis II (FAS II) pathway, is a promising target for liver stage malaria infections. Hence, pfENR inhibitors have the potential to be used as causal malarial prophylactic agents. In this study, we report the design, synthesis, structural characterization and evaluation of a new class of pfENR inhibitors. The search for inhibitors began with a virtual screen of the iResearch database by molecular docking. Hits obtained from the virtual screen were ranked according to their Glide score. One hit was selected as a lead and modified to improve its binding to pfENR; from this, a series of phenylamino acetic acid benzylidene hydrazides were designed and synthesized. These molecules were thoroughly characterized by IR, (1) H, (13) C, (15) N, 2D-NMR (COSY, NOESY, (1) H-(13) C, (1) H-(15) N HSQC and HMBC), and X-ray diffraction. NMR studies revealed the existence of conformational/configurational isomers around the amide and imine functionalities. The major species in DMSO solution is the E, E form, which is in dynamic equilibrium with the Z, E isomer. In the solid state, the molecule has a completely extended conformation and forms helical structures that are stabilized by strong hydrogen bond interactions, forming a helical structure stabilized by N-H…O interactions, a feature unique to this class of compounds. Furthermore, detailed investigation of the NMR spectra indicated the presence of a minor impurity in most compounds. The structure of this impurity was deduced as an imidazoline-4-one derivative based on (1) H-(13) C and (1) H-(15) H HMBC spectra and was confirmed from the NOESY spectra. The molecules were screened for in vitro activity against recombinant pfENR enzyme by a spectrophotometric assay. Four molecules, viz. 17, 7, 10, and 12 were found to be active at 7, 8, 10, and 12 µm concentration, respectively, showing promising pfENR inhibitory potential. A classification model was derived based on a binary QSAR approach termed recursive partitioning (RP) to highlight structural characteristics that could be tuned to improve activity.

Orthanilic acid-promoted reverse turn formation in peptides.

Orthanilic acid (2-aminobenzenesulfonic acid, (S)Ant), an aromatic ß-amino acid, has been shown to be highly useful in inducing a folded conformation in peptides. When incorporated into peptide sequences (Xaa-(S)Ant-Yaa), this rigid aromatic ß-amino acid strongly imparts a reverse-turn conformation to the peptide backbone, featuring robust 11-membered-ring hydrogen-bonding.

1-Benzoyl-3-[(2-benzylsulfanyl)phenyl]thiourea.

In the title compound, C(21)H(18)N(2)OS(2), a strong intramolecular N-H...O hydrogen bond [N...O = 2.642 (3) Å] between the amide N atom and the benzoyl O atom forms an almost planar six-membered ring in the central part of the molecule. In the crystal, molecules are packed through weak N-H...S interactions. Intra- and intermolecular hydrogen bonds and van der Waals interactions are the stabilizing forces for the crystal structure.

Phyllocladane diterpenes from Anisomeles heyneana.

New phyllocladane diterpene, phyllocladan-16α,17-dihydroxy-19-oic acid (1), together with known phyllocladane diterpene, phyllocladan-16α,19-diol (2), cembrane diterpene ovatodiolide (3), sitosteryl-3-O-ß-D-glucoside (4), and verbascoside (5), were isolated from aerial parts of Anisomeles heyneana. The structure of compound 1 was elucidated by 1D and 2D NMR analyses which included HSQC, HMBC, and nuclear overhauser effect spectroscopy (NOESY) experiments as well as X-ray crystallography. This is the first report of phyllocladane diterpenes from genus Anisomeles. Compounds 1, 3, 4, and 5 were evaluated for inhibition of Mycobacterium tuberculosis and 3 was found to exhibit anti-mycobacterial activity with IC90 6.53 µg/ml. Compounds 1, 3, and 5, at 100 µg/ml, were also evaluated for inhibition of Thp-1 cell lines, and compounds 1 and 3 showed 59.02% and 96.4% inhibitions, respectively.

Strong metal-metal coupling in mixed-valent intermediates [Cl(L)Ru(µ-tppz)Ru(L)Cl]+, L = ß-diketonato ligands, tppz = 2,3,5,6-tetrakis(2-pyridyl)pyrazine.

Five diruthenium(II) complexes [Cl(L)Ru(µ-tppz)Ru(L)Cl] (1-5) containing differently substituted ß-diketonato derivatives (1: L = 2,4-pentanedionato; 2: L = 3,5-heptanedionato; 3: L = 2,2,6,6-tetramethyl-3,5-heptanedionato; 4: L = 3-methyl-2,4-pentanedionato; 5: L = 3-ethyl-2,4-pentanedionato) as ancillary ligands (L) were synthesized and studied by spectroelectrochemistry (UV-Vis-NIR, electron paramagnetic resonance (EPR)). X-ray structural characterisation revealed anti (1, 2, 5) or syn (3) configuration as well as non-planarity of the bis-tridentate tppz bridge and strong dπ(Ru(II)) → π*(pyrazine, tppz) back-bonding. The widely separated one-electron oxidation steps, Ru(II)Ru(II)/Ru(II)Ru(III) and Ru(II)Ru(III)/Ru(III)Ru(III), result in large comproportionation constants (K(c)) of ≥10(10) for the mixed-valent intermediates. The syn-configurated (n) exhibits a particularly high K(c) of 10(12) for n = 1+, accompanied by density functional theory (DFT)-calculated minimum Ru-N bond lengths for this Ru(II)Ru(III) intermediate. The electrogenerated mixed-valent states 1(+)-5(+) exhibit anisotropic EPR spectra at 110 K with average values of 2.304-2.234 and g anisotropies Δg = g(1)-g(3) of 0.82-0.99. Metal-to-metal charge transfer (MMCT) absorptions occur for 1(+)-5(+) in the NIR region at 1660 nm-1750 nm (ε ≈ 2700 dm(3) mol(-1) cm(-1), Δν(1/2) ≈ 1800 cm(-1)). DFT calculations of 1(+) and 3(+) yield comparable Mulliken spin densities of about 0.60 for the metal ions, corresponding to valence-delocalised situations (Ru(2.5))(2). Rather large spin densities of about -0.4 were calculated for the tppz bridges in 1(+) and 3(+). The calculated electronic interaction values (V(AB)) for 1(+)-5(+) are about 3000 cm(-1), comparable to that for the Creutz-Taube ion at 3185 cm(-1). The DFT calculations predict that the Ru(III)Ru(III) forms in 1(2+)-5(2+) prefer a triplet (S = 1) ground state with ΔE (S = 0 - S = 1) ∼5000 cm(-1). One-electron reduction takes place at the tppz bridge which results in species [Cl(L)Ru(II)(µ-tppz˙(-))Ru(II)(L)Cl](-) (1˙(-)-3˙(-), 5˙(-)) which exhibit free radical-type EPR signals and NIR transitions typical of the tppz radical anion. The system 4(n) is distinguished by lability of the Ru-Cl bonds.