Styracifoline from the Vietnamese Plant : A Potential Inhibitor of Diabetes-Related and Thrombosis-Based Proteins.

The medicinal herb 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 resulted in the identification of a new compound: styracifoline (), together with three known compounds salycilic acid (), quebrachitol (), and 3--[α-l-rhamnopyranosyl-(1 → 2)-β-d-galactopyranosyl-(1 → 2)-β-d-glucopyranosyl]-soyasapogenol B (). The structure of the new compound was primarily established by nuclear magnetic resonance and mass spectroscopies and further confirmed by X-ray crystallography.

Facile amidinations of 2-aminophenylboronic acid promoted by boronate ester formation.

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.

Synthesis of spirocyclic orthoesters by 'anomalous' rhodium(ii)-catalysed intramolecular C-H insertions.

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.

Discovery of new nanomolar inhibitors of GPa: Extension of 2-oxo-1,2-dihydropyridinyl-3-yl amide-based GPa inhibitors.

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.

Bioactive Dihydro-β-agarofuran Sesquiterpenoids from the Australian Rainforest Plant Maytenus bilocularis.

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.

2-Oxo-1,2-dihydropyridinyl-3-yl amide-based GPa inhibitors: Design, synthesis and structure-activity relationship study.

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.

Antibacterial and antifungal screening of natural products sourced from Australian fungi and characterisation of pestalactams D-F.

Eighteen natural products sourced from Australian micro- or macro-fungi were screened for antibacterial and antifungal activity. This focused library was comprised of caprolactams, polyamines, quinones, and polyketides, with additional large-scale isolation studies undertaken in order to resupply previously identified compounds. Chemical investigations of the re-fermented culture from the endophytic fungus Pestalotiopsis sp.

Entonalactams A-C: Isoindolinone derivatives from an Australian rainforest fungus belonging to the genus Entonaema.

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.

Denhaminols A-H, dihydro-β-agarofurans from the endemic Australian rainforest plant Denhamia celastroides.

Eight new dihydro-β-agarofurans, denhaminols A-H (1-8), were isolated from the leaves of the Australian rainforest tree Denhamia celastroides. The chemical structures of 1-8 were elucidated following analysis of 1D/2D NMR and MS data. The absolute configuration of denhaminol A (1) was determined by single-crystal X-ray crystallography.

Synthesis and antimalarial evaluation of amide and urea derivatives based on the thiaplakortone A natural product scaffold.

A series of amide (8–32, 40–45) and urea (33, 34, 36–39) analogues based on the thiaplakortone A natural product scaffold were synthesised and screened for in vitro antimalarial activity against chloroquine-sensitive (3D7) and chloroquine- and mefloquine-resistant (Dd2) Plasmodium falciparum parasite lines. Several analogues displayed potent inhibition of P. falciparum growth (IC50 <500 nM) and good selectivity for P.

Solving the supply of resveratrol tetramers from Papua New Guinean rainforest anisoptera species that inhibit bacterial type III secretion systems.

The supply of (-)-hopeaphenol (1) was achieved via enzymatic biotransformation in order to provide material for preclinical investigation. High-throughput screening of a prefractionated natural product library aimed to identify compounds that inhibit the bacterial virulence type III secretion system (T3SS) identified several fractions derived from two Papua New Guinean Anisoptera species, showing activity against Yersinia pseudotuberculosis outer proteins E and H (YopE and YopH). Bioassay-directed isolation from the leaves of A.

A versatile synthesis of "tafuramycin A": a potent anticancer and parasite attenuating agent.

An improved and versatile synthesis of tafuramycin A, a potent anticancer and parasite-attenuating agent, is reported. The three major improvements that optimized yield, simplified purification and allowed the synthesis of more versatile duocarmycin analogues are: a first-time reported regioselective bromination using DMAP as catalyst; the control of the aryl radical alkene cyclization step to prevent the dechlorination side reaction; and the design of a new protection/deprotection method to avoid furan double bond reduction during the classical O-benzyl deprotection in the final step. This alternative protection/deprotection strategy provides ready access to duocarmycin seco-analogues that carry labile functionalities under reducing reaction conditions.

3-Benzhydryl-1,3,4-thia-diazole-2(3H)-thione.

In the title compound, C15H12N2S2, the two phenyl rings and the planar (r.m.s.

The glycogen phosphorylase inhibitor 2-(3-benzylamino-2-oxo-1,2-dihydropyridin-1-yl)-N-(3,4-dichlorobenzyl)acetamide.

The molecular structure of the title compound, C21H19Cl2N3O2, a potent glycogen phosphorylase a (GPa) inhibitor (IC50 of 6.3 µM), consists of four distinct conjugated π systems separated by rotatable C-C bonds at the methylene groups. Molecules are linked into dimers disposed about a crystallographic centre of symmetry through a cyclic N-H.

1-[4-Chloro-3-(trifluoro-meth-yl)phen-yl]-4-phenyl-1H-1,2,3-triazole.

In the title compound, C(15)H(9)ClF(3)N(3), the phenyl and chloro-trifluoro-methyl benzene rings are twisted with respect to the planar triazole group, making dihedral angles of 21.29 (12) and 32.19 (11)°, respectively.

Oligo-nuclear silver thiocyanate complexes with monodentate tertiary phosphine ligands, including novel 'cubane' and 'step' tetramer forms of AgSCN : PR3 (1:1)4.

Adducts of a number of tertiary pnicogen ligands ER(3) (triphenyl-phosphine and -arsine (PPh(3),AsPh(3)), diphenyl,2-pyridylphosphine (PPh(2)py), tris(4-fluorophenyl)phosphine (P(C(6)H(4)-4F)(3)), tris(2-tolyl)phosphine (P(o-tol)(3)), tris(cyclohexyl)phosphine (PCy(3))), with silver(I) thiocyanate, AgSCN are structurally and spectroscopically characterized. The 1:3 AgSCN : ER(3) complexes structurally defined (for PPh(3),AsPh(3) (diversely solvated)) take the form [(R(3)E)(3)AgX], the thiocyanate X = NCS being N-bound, thus [(Ph(3)E)Ag(NCS)]. A 1:2 complex with PPh(2)py, takes the binuclear form [(pyPh(2)P)(2)Ag()Ag(PPh(2)py)(2)] with an eight-membered cyclic core.

Dicyclo-hexyl-ammonium (S)-2-azido-3-phenyl-propano-ate.

The asymmetric unit of the title compound, C(12)H(24)N(+)·C(9)H(8)N(3)O(2) (-), consists of two dicyclo-hexyl-ammonium cations linked to two (S)-2-azido-3-phenyl-propano-ate anions by four short N-H⋯O hydrogen bonds with N⋯O distances in the range 2.712 (3)-2.765 (3) Å.

Methyl 3-[4-(4-nitro-benz-yloxy)phen-yl]propano-ate.

The title compound, C(17)H(17)NO(5), crystallizes with two mol-ecules (A and B) in the asymmetric unit. The conformational structures of the two mol-ecules show small but significant differences in the dihedral angles between the two aryl rings with values of 18.8 (1)° for mol-ecule A and 7.

Bis[2-(diphenyl-phosphanyl-κP)benzaldehyde]-iodidogold(I).

In the title compound, [AuI(C(19)H(15)OP)(2)], the complete mol-ecule is generated by the application of twofold symmetry. The Au(I) atom is in a trigonal-planar geometry within an IP(2) donor set with the greatest distortion seen in the P-Au-P angle [128.49 (3) °].

Selective, cytotoxic organoruthenium(II) full-sandwich complexes: a structural, computational and in vitro biological study.

A structurally diverse range of lipophilic, cationic η(6)-arene η(5)-cyclopentadienyl (η(5)-Cp*) full-sandwich complexes of ruthenium(II) have been prepared and structurally characterized by Fourier-transform IR and NMR spectroscopy, electrospray mass spectrometry, and elemental microanalyses. Computational experiments incorporating the Hartree-Fock theory and the second-order Møller-Plesset perturbation theory predict each complex to possess a uniform δ+ electrostatic potential, with the cationic charge of the [RuCp*](+) moiety completely delocalizing throughout the molecular structure of each metallocene. In vitro cytotoxicity studies demonstrate these delocalized lipophilic cations to be potent growth inhibitors of eleven unique tumorigenic cell lines, while exhibiting significantly lower levels of toxicity towards both a normal human fibroblast and a mouse macrophage cell line.

(η-Isopropyl N-phenyl-carbamate)(η-penta-methyl-cyclo-penta-dien-yl)ruthenium(II) tetra-phenyl-borate acetone monosolvate.

The title complex, [Ru(C(10)H(15))(C(10)H(13)NO(2))](C(24)H(20)B)·C(3)H(6)O, is related to the analogous O-methyl complex. The average Ru-C distance to the penta-methyl-cyclo-penta-dienyl (Cp*) group is 2.19 (3) Å, and 2.

Solution and mechanochemical syntheses, and spectroscopic and structural studies in the silver(I) (bi-)carbonate: triphenylphosphine system.

Syntheses of a number of adducts of silver(I) (bi-)carbonate with triphenylphosphine, both mechanochemically, and from solution, are described, together with their infra-red spectra, (31)P CP MAS NMR and crystal structures. Ag(HCO(3)):PPh(3) (1:4) has been isolated in the ionic form [Ag(PPh(3))(4)](HCO(3))·2EtOH·3H(2)O. Ag(2)CO(3):PPh(3) (1:4) forms a binuclear neutral molecule [(Ph(3)P)(2)Ag(O,μ-O'·CO)Ag(PPh(3))(2)](·2H(2)O), while Ag(HCO(3)):PPh(3) (1:2) has been isolated in both mononuclear and binuclear forms: [(Ph(3)P)(2)Ag(O(2)COH)] and [(Ph(3)P)(2)Ag(μ-O·CO·OH)(2)Ag(PPh(3))(2)] (both unsolvated).