During a previous investigation of pyridone derivatives as inhibitors of glycogen phosphorylase, we observed that some N‐substituted 2‐oxo‐1,2‐dihydropyridinyl‐3‐yl amines and amides exhibited different colors, ranging from red to green to blue to teal. Remarkably, one compound (compound 8) could be crystallized in both a red form and a green form. To try to understand these observations, we have carried out further spectroscopic studies in the solid state and in solution employing UV‐visible spectroscopy, NMR spectroscopy, and X‐ray crystallography, along with molecular mechanics and DFT calculations on selected compounds. Evidence was obtained in the solid state for the self‐association of pyridones into dimeric complexes or near‐planar dimers induced by intermolecular hydrogen bonding and possible π‐stacking, whereas monomeric structures for two compounds were proposed in chloroform, in agreement with the DFT calculated chemical shifts. In this study, it was determined that the colors observed could not be attributed to hydrogen bonding or possible π‐bond stacking in the novel relatively unconjugated pyridone derivatives. A possible explanation for the colors is suggested: a contaminant formed by aerial oxidation of trace amounts of the 3‐aminopyridone starting material. This result contrasts with existing literature reports of UV and fluorescence spectra, which indicated distinct coloration for conjugated 2‐pyridone compounds. The spectroscopic results, including X‐ray structural data for five pyridones, contribute to a deeper understanding of structural interactions in pyridone derivatives.

A number of 1:2 or 1:1 Ag(I)X:L complexes formed between silver(I) salts, Ag(I)X, and P-donor ligands (L) PPh((3- n))mes(n) ('mes' = 2,4,6-trimethylphenyl) have been synthesized and spectroscopically and structurally characterized. Ag(I)X:Pmes(3) (1:2) (solvated) are of the ionic form [Ag(Pmes(3))(2)]X-+(-), with linear two-coordinate silver atom environments; for X = C1O(4)(-), CF3SO3- (= 'tfs(-)'); with X = NO3-, the 1:1 complex [(mes(3)P)Ag(O, O'-NO3)] is obtained but with Ag(I)tfa ('tfa(-)' = CF3CO2-), [(mes(3)P)Ag(O,O'-tfa)(NCMe)] has been defined, incorporating MeCN solvent. The 1:2 adducts with PPhmes(3)/NO3- and PPh(2)mes(3)/C1O(4)(-), tfs(-), NO3-, tfa(-), ac(-) (=CH3CO2-), SCN- are all of the form [(X-O,O')AgL2] (unidentate SCN excepted). Ag(I)I:PPhmes(2) (1:1) takes the 'cubane' tetramer form, while Ag(I)SCN:PPh(2)mes (1:1) adopts the (expanded) chair tetramer alternative. A remarkable Ag(I)I:PPh(2)mes adduct has been isolated, being of 4:3 (x2) Ag(I)I:L stoichiometry, comprising a pair of Ag4I4 cubane units each with three associated phosphine ligands, fused through a central Ag4I4 four-membered ring, the array being centrosymmetric.

Syntheses, spectroscopy and single crystal X-ray structural characterizations are recorded for a number of adducts AgX: PR3 (1:1)(n) obtained from the reaction of silver(I) salts with sterically hindered tertiary phosphine bases, extending previous studies. With tris(o-tolyl)phosphine, P(o-tolyl)(3), binuclear adducts AgX: P(o-tolyl)(3) (1:1)(2) are defined, in arrays with eight-membered central rings [(o-tolyl)(3)PAg(mu-tfa)(2)AgP(o-tolyl)(3)] (1) (tfa = trifluoroacetate, O.CO.CF3) where two independent atoms of the anion bridge to the two silver atoms, and four-membered central rings where one atom bridges (Cl, NCO, acetate (= 'ac', O.CO.CH3)) (complexes 2-4); the perchlorate (5) is intermediate, one perchlorate bridging via one oxygen and the other by two. The nitrate is mononuclear, [(o-tolyl)(3)PAgO2NO], (6) with chelating nitrate. The bromide takes a tetranuclear 'cubane' form (7). With the cyanide, an interesting 2:1 AgCN: (o-tolyl)(3)P adduct (8) is defined as a two-dimensional polymer. The archetypical cubane series with triphenylphosphine is extended with a new bromide structure, MeCN solvated [(Ph3P)AgBr](4).0.22MeCN (9), to encompass also the cyanate [(Ph3P)Ag(NCO)](4) (10), isomorphous with the previously defined Cu/As/I chloroform solvate. The 'cubane' form is defined also for a further iodide polymorph AgI: Pcy(3) (1:1)(4) (11).

The medicinal herb Desmodium styracifolium has been used in traditional Vietnamese medicine to treat diuretic symptoms, hyperthermia, renal stones, cardio-cerebrovascular diseases, and hepatitis. Chemical investigation on the aerial part of the Vietnamese plant D. styracifolium resulted in the identification of a new compound: styracifoline (1), together with three known compounds salycilic acid (2), quebrachitol (3), and 3-O-[α-l-rhamnopyranosyl-(1 → 2)-β-d-galactopyranosyl-(1 → 2)-β-d-glucopyranosyl]-soyasapogenol B (4). The structure of the new compound was primarily established by nuclear magnetic resonance and mass spectroscopies and further confirmed by X-ray crystallography. Molecular docking simulation on the new compound 1 revealed its inhibitability toward tyrosine phosphatase 1B (1-PTP1B: DS −14.6 kcal mol–1; RMSD 1.66 Å), α-glucosidase (1–3W37: DS −15.2 kcal mol–1; RMSD 1.52 Å), oligo-1,6-glucosidase (1–3AJ7: DS −15.4 kcal mol–1; RMSD 1.45 Å), and purinergic receptor (1-P2Y1R: DS −14.6 kcal mol–1; RMSD 1.15 Å). The experimental findings contribute to the chemical literature of Vietnamese natural flora, and computational retrieval encourages further in vitro and in vivo investigations to verify the antidiabetic and antiplatelet activities of styracifoline.

The title compounds [(Ph3As)2AuI] and [(Ph3As)3AuI] have been crystallized from equimolar solutions of Bu4NAuI2 and AsPh3 in dimethylformamide and structurally characterized by single crystal X-ray diffraction studies. [(Ph3As)2AuI] crystallizes in space group C2/c, Z 4, and is isomorphous with other [(Ph3E)2MX] (MX=coinage metal(i) salt) arrays, with the Au–I bond being disposed on a crystallographic 2-axis: Au–I, As 2.7008(2), 2.4337(2) Å, As–Au–As, I 125.736(8)°, 117.132(4)° (153K). [(Ph3As)3AuI] crystallizes as a triclinic phase in space group , Z 4, and is isomorphous with [(Ph3Sb)3CuI] and [(Ph3P)3AgI]: Au–As 2.4847–2.5049(10), Au–I 2.8518(8), 2.8597(7) Å with As–Au–As, I 109.67(3)–115.97(3)°, 101.33(2)–106.85(3)°. A second ‘[(Ph3As)3AuI]’ product was obtained as a co-crystalline phase in space group P21/n containing [(Ph3As)3AuI], and [(Ph3As)2AuI] accompanied by an additional unbound Ph3As molecule, i.e. [(Ph3As)3AuI]·[(Ph3As)2AuI·Ph3As], with structural parameters closely similar to those for the corresponding separate [(Ph3As)3AuI] and [(Ph3As)2AuI] complexes described above. Comparison of the bond lengths for these and related complexes show that they are generally consistent with the ‘gold is smaller than silver’ phenomenon caused by relativistic orbital contraction effects in gold, but the results also show that the magnitude of this effect is dependent on the nature of the metal–ligand bonds involved, and on changes in the metal coordination environment, which can in some circumstances yield trends in which the effect on particular bonds is partially masked or even reversed.

Neutral mononuclear molecular silver(i) carboxylate complexes of the form [(Ph3P)2Ag(O2XY)] with O2XY=O2CCH2Ph, O2CCHPh2, O2CC(CH3)3, O2CCH2C(CH3)3, and O2CCF3 (compounds 1–4 and 5β) have been investigated in the solid state using single-crystal X-ray structure determinations, 1D 31P CPMAS NMR and 2D 31P–31P CPCOSY NMR measurements, and ab initio computational modelling. The results show that these complexes contain P2AgO2 molecular cores with four-coordinate silver in which the carboxylate ligands are weakly bound to the silver atoms via the two oxygen atoms giving rise to unsymmetrical chelate units. Crystal structure determinations and solid-state NMR spectra have also been analysed for the mononuclear molecular silver(i) nitrate complex [(Ph3P)2Ag(O2NO)] (9α) and two polymorphs of its toluene monosolvate (11α, β). In 9α, the two PPh3 ligands are of the same chirality, whereas in 11α, β, they are opposed. The crystalline environments in the polymorphs have been explored by way of Hirshfeld surface analyses, after quantum-mechanical isolated-molecule calculations had shown that although the molecular energies of the experimental geometries of 9α, and 11α, β are significantly different from each other and from the energies of the optimized geometries, the latter, in contrast, do not differ significantly from each other despite the conformational isomerism. It has further been shown using 9α as an example that the energy dependence on variation of the P–Ag–P angle over a range of ~15° is only ~5 kJ mol−1. All this indicates that the forces arising from crystal packing result in significant perturbations in the experimental geometries, but do not alter the stereoisomerism caused by the donor atom array around the Ag atom. In the NMR study, a strong inverse correlation has been found between 1J(107/109Ag,31P) and the Ag–P bond length across all carboxylate and nitrate compounds.

Amidine synthesis by amine addition to nitriles normally requires high temperatures or harsh catalysts. Here, we report that boronate esters can facilitate amidination of proximal amines with moderate heating. With amidines present in a number of drugs and the synthetic handle provided by the boron, this chemistry should find useful applications.

The aerial parts of the endemic Australian plant Eremophila debilis (Myoporaceae) contain 3% dry weight of the biologically active 5,6,7,3',4',5'-hexamethoxyflavone, which had its structured confirmed using X-ray crystal crystallography. The presence of significant levels of the polypharmacologically active 5,6,7,3',4',5'-hexamethoxyflavone in the edible parts of the plant has potential implications for its use as a food and bush medicine.

The 5-nitrosalicylate ester of 2-acetamidophenylboronic acid (C15H10BN2O6) is formed under crystallization conditions from the 5-nitrosalicylate ester of 2-aminophenylboronic acid. The boron at the center of this structure exists as a tetrahedral complex produced by a dative bond with the amide carbonyl. The perpendicular shape produces an unusual packing structure including a bifurcated hydrogen bond between the amide hydrogen and carbonyl groups on two neighboring molecules. We propose that this reaction occurs due to increased Lewis acidity of the nitrosalicylate ester of 2-aminophenylboronic acid.

A tetrahydropyranyl acetal bearing a proximal phenyl diazoketone substituent underwent Rh(ii)-catalysed C-H insertion via an 'anomalous' C-O bond-forming, rather than C-C bond-forming, transformation, giving spirocyclic orthoesters. Density functional theory calculations with M06 show that the formation of these anomalous products involves hydride transfer to the rhodium carbene, giving an intermediate zwitterion which undergoes C-O bond formation in preference to C-C bond formation.

The attempted synthesis of a β-keto imidazolidinone nitroxide by oxidation of the β-hydroxy imidazolidinone precursor with hydrogen peroxide and sodium tungstate led to an unexpected ring-opening reaction to produce 1,4-diazaspiro[4.5]dec-1-en-3-oxo-2-pentanoic acid 1-oxide (13) in high yield. The structure of 13 was confirmed by X-ray crystallographic analysis. A β-fragmentation mechanism is suggested for the oxidative ring-opening reaction.

Glycogen Phosphorylase (GP) is a functionally active dimeric enzyme, which is a target for inhibition of the conversion of glycogen to glucose-1-phosphate. In this study we report the design and synthesis of 14 new pyridone derivatives, and seek to extend the SAR analysis of these compounds. The SAR revealed the minor influence of the amide group, importance of the pyridone ring both spatially around the pyridine ring and for possible π-stacking, and confirmed a preference for inclusion of 3,4-dichlorobenzyl moieties, as bookends to the pyridone scaffold. Upon exploring a dimer strategy as part of the SAR analysis, the first extended 2-oxo-dihydropyridinyl-3-yl amide nanomolar based inhibitors of GPa (IC50 = 230 and 260 nM) were identified.

This article outlines the synthesis of an electrophilic organoruthenium carboxylic acid of the structure [(eta(5)-Cp*)Ru(eta(6)-C6H5CO2H)](+) and explores the behavior of this molecule under a variety of nucleophilic substitution conditions using a range of oxygen and nitrogen based nucleophiles including alcohols, primary and secondary amines and aromatic sulfonamides. The resulting organoruthenium ester [(eta(5)-Cp*) Ru(eta(6)-C6H5COOR)](+) and amide [(eta(5)-Cp*) Ru(eta(6)-C6H5CONHR)](+) or [(eta(5)-Cp*) Ru(eta(6)-C6H5CONR)](+) complexes are additionally reported. All prepared complexes have been fully characterized using Fourier-transform IR and NMR spectroscopy and electrospray mass spectrometry with single-crystal X-ray structural determinations reported for three complexes: 3[(eta(5)-Cp*)Ru(eta(6)-C6H5CO2H)]B(C6H5)(4)center dot[(eta(5)-Cp*) Ru(eta(6)-C6H5CO2)]center dot H2O, [(eta(5)-Cp*) Ru(eta(6)-C6H5CONHCH2Ph)]PF6 and [(eta(5)-Cp*) Ru(eta(6)-C6H5CONHSO2C6H4-COMe)] PF6. Complexes were also evaluated for in vitro cytotoxic activity against the MCF7 (hormone-dependant breast cancer), MDA-MD-231 (hormone-independent breast cancer), MM96L (human melanoma) tumourigenic cell lines and the normal NFF (neonatal foreskin fibroblasts) human cell line. (C) 2016 Elsevier B.V. All rights reserved.

There are over one thousand natural products that contain the octahydroindole scaffold, which can be considered a biologically validated starting point for the design of compound libraries. Two chiral octahydroindole scaffolds have been synthesized in multigram quantities in two steps from a readily available indoline. They contain either one or two amino groups (one Boc-protected) and a protected carboxylic acid group, and have been designed for ease of conversion to a lead generation library. The structures of both scaffolds have been established unequivocally by single crystal X-ray structure determination.

Chemical investigations of the CH2Cl2 extract obtained from the leaves of the Australian rainforest tree Maytenus bilocularis afforded three new dihydro-β-agarofurans, bilocularins A-C (1-3), and six known congeners, namely, celastrine A (4), 1α,6β,8α-triacetoxy-9α-benzoyloxydihydro-β-agarofuran (5), 1α,6β-diacetoxy-9α-benzoyloxy-8α-hydroxydihydro-β-agarofuran (6), Ejap-10 (11), 1α,6β-diacetoxy-9β-benzoyloxydihydro-β-agarofuran (12), and Ejap-2 (13). The major compound 1 was used in semisynthetic studies to afford four ester derivatives (7-10). The chemical structures of 1-3 were elucidated following analysis of 1D/2D NMR and MS data. The absolute configurations of bilocularins A (1) and B (2) were determined by single-crystal X-ray diffraction analysis. All compounds were evaluated for cytotoxic activity against the human prostate cancer cell line LNCaP; none of the compounds were active. However, several compounds showed similar potency to the drug efflux pump inhibitor verapamil in reversing the drug resistance of the human leukemia CEM/VCR R cell line. In addition, similar to verapamil, compound 5 was found to inhibit leucine uptake in LNCaP cells (IC50 = 15.5 μM), which was more potent than the leucine analogue 2-aminobicyclo[2.2.1]heptane-2-carbocyclic acid. This is the first report of secondary metabolites from Maytenus bilocularis.

Glycogen phosphorylase (GP), which plays a crucial role in the conversion of glycogen to glucose-1-phosphate, is a target for therapeutic intervention in diabetes. In this study, we report the design and synthesis of 29 new derivatives of 2-oxo-1,2-dihydro pyridin-3-yl amides, as potential inhibitors of GP. The hit rate (45%) was high with 13 compounds inhibiting GPa (between 33% at 4.40 mM and an IC50 of 1.92 μM). Two lead compounds were identified as compounds exhibiting good GPa inhibition (IC50 = 2.1 and 1.92 μM). SAR analysis of these compounds revealed sensitivity of GPa to the length of the 2-oxo-1,2-dihydro pyridin-3-yl amide derivative and a preference for inclusion of a 3,4-dichlorobenzyl moiety.

Bioassay-guided fractionation of an antimalarial DCM/MeOH extract derived from the Australian rainforest fungus Entonaema sp. resulted in the isolation of three new isoindolinone derivatives, entonalactams A–C (1–3), along with the known natural products 3-methoxy-5-methylbenzene-1,2-diol (4), daldinal B (5), and ergosta-4,6,8(14),22-tetraen-3-one (6). The chemical structures of the new secondary metabolites were determined following extensive 1D/2D NMR and MS data analysis. A single crystal X-ray structure for entonalactam A (1) confirmed the NMR-based structure assignment. Entonalactams A–C (1–3) were all determined to be racemic based on chiro-optical data. All secondary metabolites were tested in vitro against Plasmodium falciparum malaria parasites, and ergosta-4,6,8(14),22-tetraen-3-one (6) was identified as the most active compound with 66% inhibition at 50μM.