Pyran Moiety Research Articles

Synthesis and study of benzofuran-pyran analogs as BMP-2 targeted osteogenic agents

Twenty-four novel benzofuran-pyran derivatives were synthesized and evaluated for their anti-osteoporotic activity in primary cultures of rat calvarial osteoblasts in vitro. Among all the compounds screened for the alkaline phosphatase activity, three compounds 4e, 4j and 4k showed potent activity at picomolar concentrations in osteoblast differentiating stimulation. Additionally, these compounds were found effective in mineralization, assessed by alizarin red-S staining assay. Compounds were again validated through a series of other in vitro experiments. Moreover, molecular dynamics simulations demonstrated that both benzofuran and pyran moieties are requisite to fit into the active site of BMP-2 receptor, a key target of the osteogenic agents. The obtained results strongly convey that compound 4e is a potential bone anabolic agent among synthesized series, which can be further explored as a drug lead for treating osteoporosis.

Facile Synthesis of the O-Functionalized Ladder-Type Dipyran Building Block and Its Application in Polymer Solar Cells.

A new centrosymmetrical dipyran unit (DTDP) is successfully prepared by means of an efficient and universal way, and a series of PDTDP polymers have been prepared so as to assess their potential application in organic photovoltaic. The function of pyran moiety is not merely limited to tune the electron-donating roles and energy levels but it also contributes to solubility improvement. Interestingly, all pyran-based polymers displayed wide absorption ranging from 350 to 780 nm, but varied aggregation phenomena are observed. Furthermore, the quantum chemistry calculations for dimers, morphology study and grazing-incidence wide-angle X-ray scattering analysis for blend films have been utilized to understand the variations at photovoltaic performances. Finally, PDTDP-4 achieved the highest power conversion efficiency of 7.26% ( Voc = 0.72 V, FF = 0.66, and Jsc = 15.30 mA/cm2), demonstrating promising usage for high-efficiency polymer donors in polymer solar cells. In all, not only a promising dipyran building block is provided by this study, more dipyran derivatives and polymers could be prepared via this facile synthetic route.

Synthesis and special characterization through X-ray analysis of 1,8-dioxooctahydroxanthenes

Pyran moiety containing heterocyclic compounds have the capability for binding to either side to cyclohex-2-enone rings and to form xanthene derivatives (1,8-dioxooctahydroxanthenes also known as xanthenodiones). These xanthene derivatives display a wide range of biological activities and find applications in laser technologies and photodynamic therapy. This paper describes the preparation, X-ray structural analysis, and theoretical investigation of a series of 1,8-dioxooctahydroxanthenes. The compounds were synthesized via Knoevenagel condensation between different aldehydes and β-diketones. The reactions were performed free of solvents and the 1,8-dioxooctahydroxanthenes were obtained in good yields (70−92%). All the compounds were fully characterized by NMR and IR spectroscopy as well as mass spectrometry. Among the synthesized compounds, seven had their crystal structures elucidated for the first time. In all the new crystal structures, the three fused rings did form an almost completely planar xanthenodione core, except for the side rings that adopt half-chair conformation with both carbons at the flaps oriented toward to the aromatic substituent, or with one of the two carbons pointing opposite to the substituent. Another conformational difference among the new compounds investigated by X-ray diffraction resides in the rotation around the bond axis connecting the xanthenodione core to its aromatic substituent. It was found that different bent levels resulted from weak intermolecular contact patterns. In addition, theoretical calculations for single molecule and dimmers have provided insights into the balance between intramolecular and intermolecular forces driving both conformational features.

Synthesis of the C1–C9, C11–C19 Pyran Core and C19–C24 Fragments­ of Macrolactin 3

We describe herein an efficient synthesis of the C1–C9, C11–C19 pyran moiety and C18–C24 core fragments of macrolactin 3. The prominent features of this work include construction of the Z-double bond of the 1,3-(Z,E)-diene system utilizing Horner–Wadsworth–Emmons­ reaction under Still–Gennari conditions. A Sharpless asymmetric epoxidation and subsequent epoxide opening under BF3·OEt2 conditions were applied to generate the stereogenic centers at C15 and C16, oxa-Michael addition and Jacobsen resolution facilitate the synthesis of the fragments.

Synthesis, spectroscopic characterization, and crystal structure of a novel indoline derivative

A new indoline derivative, tert-butyl 2′-amino-3′-cyano-6′-methyl-2-oxospiro[indoline-3,4′-pyran]-5′-carboxylate is eco-friendly synthesized, and its spectral properties and X-ray crystal structure are studied. In the molecule, the oxindole and pyran moieties are perpendicular to each other. The crystal structure is stabilized by intermolecular N−H···O and intramolecular C−H···O hydrogen bonds. Centrosymmetric dimer units are formed by intermolecular N−H···O hydrogen bonds. In addition, one C−H···π interaction is also observed.

Coumarin-Spiropyran Dyad with a Hydrogenated Pyran Moiety for Rapid, Selective, and Sensitive Fluorometric Detection of Cyanide Anion.

We synthesized a coumarin-spiropyran dyad with a hydrogenated pyran moiety (2), behaving as an off-on type fluorescent receptor for rapid, selective, and sensitive detection of cyanide anion (CN(-)) in aqueous media. The receptor itself shows almost no fluorescence with a quantum yield < 0.01, due to the delocalization of π-electrons over the molecule. Selective nucleophilic addition of CN(-) to the spirocarbon of the molecule rapidly promotes spirocycle opening within only 3 min. This leads to localization of π-electrons on the coumarin moiety and exhibits strong light-blue fluorescence at 459 nm with very high quantum yield (0.52). As a result of this, the receptor facilitates rapid, selective, and sensitive fluorometric detection of CN(-) as low as 1.0 μM.

Indenopyrans - synthesis and photoluminescence properties.

New indeno[1,2-c]pyran-3-ones bearing different substituents at the pyran moiety were synthesized and their photophysical properties were investigated. In solution all compounds were found to be blue emitters and the trans isomers exhibited significantly higher fluorescence quantum yields (relative to 9,10-diphenylanthracene) as compared to the corresponding cis isomers. The solid-state fluorescence spectra revealed an important red shift of λmax due to intermolecular interactions in the lattice, along with an emission-band broadening, as compared to the solution fluorescence spectra.

Accidental degeneracy in the spiropyran radical cation: charge transfer between two orthogonal rings inducing ultra-efficient reactivity.

Photochromism of the spiropyran radical cation to the corresponding merocyanine form is investigated by a combination of electrochemical oxidation, UV/vis absorption spectroscopy, spectroelectrochemistry and first-principles calculations (TD-DFT, CAS-SCF and CAS-PT2). First, we demonstrate that the ring-opening of mono-spiropyrans occurs upon one-electron oxidation and that it can be driven photochemically as well as thermally, with trapping of the merocyanine by protonation. Second, in order to explain this experimentally observed spectroelectrochemical behaviour we suggest a theoretical mechanism based on the reactivity of the two lowest electronic excited-states, which promotes effective electron transfer from the indoline (nitrogen-ring) to the pyran (oxygen-ring) moieties (and vice versa) through a conical intersection seam of degeneracy. Characterisation of the minimum energy conical intersection on this crossing revealed that it presents a rare diabatic trapping topology. The excited state molecule cannot escape from crossing the intersection seam due to the presence of only one degeneracy-lifting coordinate that efficiently channels into the formation of the merocyanine photoproduct, so giving rise to a "kitchen sink" funnel-like effect. Therefore, assuming rapid relaxation after vertical excitation to a higher electronic state, photoconversion cannot be avoided in the D1 electronic state, which rationalises the remarkably efficient visible light driven excited-state reactivity observed experimentally.

Synthesis, characterization, and biological evaluation of new quinazolin-4-one derivatives hybridized with pyridine or pyran moiety

A new series of 2-(furan-2-yl)-4-oxoquinazolin-3-phenyl derivatives hybridized with pyridine 3a–d, 4a–d or pyran moiety 5a–d were synthesized; their structures were confirmed by spectral and elemental analysis. Cytotoxicity was evaluated on three cancer cell lines (HEPG2, HCT116 and MCF7) using the sulphorodamine-B assay method and doxorubicin as a reference drug. Compound 5d showed a closely similar activity to doxorubicin on MCF7; their IC50 values are 4.6 and 4.4 nmol/mL, respectively. In addition, compounds 4b and 4c exhibited a closely similar activity to doxorubicin on HEPG2 cancer cells; their IC50 values expressed in nmol/mL are 6.6, 6.7, and 5.7, respectively. Moreover, compound 4b (IC50 = 1.2 nmol/mL) was four times more potent than doxorubicin (IC50 = 4.8 nmol/mL) on HCT116, and compound 5d (IC50 = 0.2 nmol/mL) revealed potency equal to 24 times the potency of doxorubicin on the same cancer cell line. The most active compounds were screened against EGFR TK, and results showed that compound 5d was the most potent inhibitor; its percentage of inhibition was 95.6. Furthermore, compound 5d was docked into the EGFR binding site to explore its possible interactions with EGFR TK.

6-Amino-3-methyl-4-(3,4,5-tri-meth-oxy-phen-yl)-2,4-di-hydro-pyrano[2,3-c]pyrazole-5-carbo-nitrile.

In the title compound, C17H18N4O4, the dihedral angle between the benzene ring and 2,4-di­hydro­pyrano[2,3-c]pyrazole ring system is 89.41 (7)°. The pyran moiety adopts a strongly flattened boat conformation. In the crystal, mol­ecules are linked by N—H⋯N, N—H⋯O, C—H⋯N and C—H⋯O hydrogen bonds into an infinite two-dimensional network parallel to (110). There are π–π inter­actions between the pyrazole rings in neighbouring layers [centroid–centroid distance = 3.621 (1) Å].

ChemInform Abstract: Construction and Functionalization of Pyranone Ring Fused with Pyran Moiety: Design and Synthesis of Novel Pyrano[4,3‐b]pyran‐5(4H)‐ones as Potential Inhibitors of Sirtuins.

AbstractA broad range of the functionalized title compounds is synthesized and evaluated for their inhibitory activity.

Synthesis and biological studies of steroidal pyran based derivatives

Steroid based cancer chemotherapeutic agents of the type 2′-amino-3′-cyanocholest-6-eno[5,7-de]4H-pyrans (1c–3c) have been synthesized and characterized by the various spectroscopic and analytical techniques. The DNA binding studies of compounds (1c–3c) with CT DNA were carried out by UV–vis and fluorescence spectroscopy and gel electrophoresis. The compounds (1c–3c) bind to DNA preferentially through electrostatic and hydrophobic interactions with Kb values found to be 5.4×103, 2.3×103M−1 and 1.97×103M−1, respectively indicating the higher binding affinity of compound (1c) towards DNA. The molecular docking study suggested that the electrostatic interaction of compounds (1c–3c) in between the nucleotide base pairs is due to the presence of pyran moiety in steroid molecule. All the compounds (1c–3c) cleave supercoiled pBR322 DNA via hydrolytic pathway, as validated by T4 DNA ligase assay. The compounds (1c–3c) were screened for in vitro cytotoxicity against the cancer and non-cancer cells SW480, A549, HepG2, HeLa, MCF-7, HL-60, DU-145, NL-20, HPC and HPLF by MTT assay. The compounds (1c–3c) were tested for genotoxicity (comet assay) involving apoptotic degradation of DNA and was analyzed by agarose gel electrophoresis and visualized by ethidium bromide staining. The results revealed that compound (1c) has better prospectus to act as cancer chemotherapeutic candidate which warrants further in vivo anticancer investigations.

Synthesis of Stereochemically and Skeletally Diverse Fused Ring Systems from Functionalized C-Glycosides

A diversity-oriented synthesis (DOS) strategy was developed for the synthesis of stereochemically diverse fused-ring systems containing a pyran moiety. Each scaffold contains an amine and methyl ester for further diversification via amine capping and amide coupling. Scaffold diversity was evaluated in comparison to previously prepared scaffolds by a shape-based principal moments of inertia (PMI) analysis.

Construction and functionalization of pyranone ring fused with pyran moiety: Design and synthesis of novel pyrano[4,3-b]pyran-5(4H)-ones as potential inhibitors of sirtuins

Novel pyrano[4,3-b]pyran-5(4H)-one based small molecules were designed as potential inhibitors of sirtuins (i.e., yeast sir2, a homolog of human SIRT1). Elegant synthesis of these compounds was performed via a multi-step sequence consisting of MCR, Sandmeyer type iodination, Sonogashira type coupling followed by iodocyclization and then Pd-mediated various C–C bond forming reactions. The overall strategy involved the construction of a pyran ring followed by the fused pyranone moiety and subsequent functionalization at C-8 position of the resultant core pyrano[4,3-b]pyran-5(4H)-one framework. The crystal structure analysis of a representative iodolactonized product (6d) is presented. Some of the synthesized compounds showed promising inhibitory activities when tested against yeast sir2 in vitro. The compound 6g showed dose dependent inhibition (IC50=78.05μM) of yeast sir2 and good interactions with this protein in silico.

Experimental design optimization for electrochemical removal of gentamicin: toxicity evaluation and degradation pathway

Electrochemical degradation of gentamicin was achieved using a laboratory scale electrochemical reactor by optimizing pH, current density and treatment time. A two step statistical optimization was performed as per factorial design and center composite design (CCD). A Pareto chart was used for selecting statistically significant effects and an analysis of variance (ANOVA) table indicated significant curvature. Thus adding additional experimental runs improved the model fitting through a second order model. Maximum degradation was predicted at a pH of 6.7, 70 A m(-2) and 45 min. The experimental data fitted well through a reduced quadratic model with R(2) equal to 0.945. The toxicity of degradation products as determined by disc diffusion assay employing Pseudomonas aeruginosa strain was found to be reduced by 55%. The degradation pathway of gentamicin was studied using mass spectral (MS) analysis. Pure gentamicin showed a molecular ion peak at m/z 478 ([M + 1](+)), and after addition of NaCl as electrolyte, the mass peak was observed at m/z 523. After 15 min of electrochemical treatment, a new peak appeared at m/z 316 due to the loss of one pyran moiety. After 45 min of electrochemical treatment, another peak appeared at m/z of 478 due to loss of two Na(+) from gentamicin.

ChemInform Abstract: Expeditious Synthesis of the Cores of Naturally Occurring Cyclic Polyethers Using a Divergent Ring Rearrangement Metathesis Strategy.

AbstractThe expeditious and stereocontrolled preparation of the bicyclic cores of cyclic polyethers of the dysiherbaine and acetogenin families includes an unprecedented ring rearrangement metathesis, involving the pyran moiety of oxabicyclo[3.2.1]octenes.

Red Fluorescent 4-(Dicyanomethylene)-2- (1-pentylbicyclo[2,2,2]oct-4-yl)-6-(1,1,2,2,7,7-hexamethyljulolidyl-9-enyl)-4H-pyran (DCHMJPB) for Organic Light-Emitting Diodes (OLEDs)

An efficient red fluorescent compound, 4-(Dicyanomethylene)-2-(1-pentylbicyclo- [2,2,2]oct-4-yl)-6-(1,1,2,2,7,7-hexamethyljulolidyl-9-enyl)-4H-pyran (DCHMJPB) containing two additional methyl groups on julolidine moiety and 1-pentylbicyclo- [2,2,2]octyl group on pyran moiety, was synthesized and characterized. In this red emitter, the bulky groups such as two additional methyl groups and 1-pentylbicyclo- [2,2,2]octyl group were introduced to increase the steric hindrance between the red emitters and prevent concentration quenching. In particular, in an efficient red device containing emitter DCHMJPB as a dopant, a luminous and power efficiency of 3.76 cd/A and 1.97 lm/W was achieved, respectively, at 20 mA/cm2 with the CIE coordinates of (x = 0.56, y = 0.42) at 7.0V.

Red Fluorescent DCM Derivatives with the Bulky-substituents on Pyran and Julolidine Moieties for Organic Light-Emitting Diodes (OLEDs)

In most DCM type emitters, concentration quen-ching due to excimer and exciplex formation dramaticallyreduces EL performance. Among those, 4-(dicyanomethyl-ene)-2-tert-butyl-6-(1,1,7,7-tetramethyljulolidyl-9-enyl)-4 H-pyran (DCJTB) represents one of the most efficient fluore-scent red emitting materials for OLEDs. In DCJTB, thebulky substituents such as four methyl groups on julolidinemoiety and tert-butyl group on pyran moiety of DCM back-bone are incorporated to prevent concentration quenchingbetween the emitting materials, which lead to the improvedEL efficiencies of devices using them.

Modified 4-(dicyanomethylene)-2- tert-butyl-6-(1,1,7,7-tetra-methyljulolidyl-9-enyl)-4 H-pyran-containing red fluorescent emitters for efficient organic light-emitting diodes

Efficient red fluorescent compounds Red 1 and Red 2 based on bulky bicyclo[2,2,2]octane groups in the pyran moiety and tert-butyl or isopropyl group in the julolidine moiety of the 4-(dicyanomethylene)-2- tert-butyl-6-(1,1,7,7-tetra-methyljulolidyl-9-enyl)-4 H-pyran (DCJTB) skeleton were synthesized and characterized. As red-emitting dopants in an Alq 3 single-host emitting system, Red 1 and Red 2 exhibited improved color purity and enhanced luminous efficiency compared to DCJTB. Moreover, a device using Red 1 as a dopant in a rubrene–Alq 3 co-host emitting system exhibited improved electroluminescence performance with a luminous efficiency and power efficiency of 6.89 cd/A and 3.09 lm/W at 20 mA/cm 2, respectively, and CIE x,y coordinates of ( x = 0.64, y = 0.36) at 7.0 V, approaching saturated red emission.

Cloning and Elucidation of the FR901464 Gene Cluster Revealing a Complex Acyltransferase-less Polyketide Synthase Using Glycerate as Starter Units

FR901464, an antitumor natural product, represents a new class of potent anticancer small molecules targeting spliceosome and inhibiting both splicing and nuclear retention of pre-mRNA. Herein we describe the biosynthetic gene cluster of FR901464, identified by degenerate primer PCR amplification of a gene encoding the 3-hydroxy-3-methylglutaryl-CoA synthase (HCS) postulated to be involved in the biosynthesis of a β-branched polyketide from Pseudomonas sp. No. 2663. This cluster consists of twenty open reading frames (ORFs) and was localized to 93-kb DNA segment, and its involvement in FR901464 biosynthesis was confirmed by gene inactivation and complementation. FR901464 is biosynthesized by a hybrid polyketide synthase (PKS)/nonribosomal peptide synthetase (NRPS), HCS, and acyltransferases (AT)-less system. The PKS/NRPS modules feature unusual domain organization including multiple domain redundancy, inactivation, and tandem. Biochemical characterization of a glyceryl transferase and an acyl carrier protein (ACP) in the start module revealed that it incorporates D-1,3-bisphosphoglycerate, which is dephosphorylated and transferred to ACP as the starter unit. Furthermore, an oxidative Baeyer-Villiger reaction followed by chain release was postulated to form a pyran moiety. On the basis of in silico analysis and genetic and biochemical evidances, a biosynthetic pathway for FR901464 was proposed, which sets the stage to further investigate the complex PKS biochemically and engineer the biosynthetic machinery for the production of novel analogues.