Enantioselective alkynylation to aldimines catalyzed by chiral 2,2′-di(2-aminoaryloxy)-1,1′-binaphthyl-copper(I) complexes

The enantioselective alkynylation of aldimines with terminal acetylenes catalyzed by chiral Cu(I) complexes with (R)-2,2′-di(2-aminoaryloxy)-1,1′-binaphthyl ligands (7) was examined. Chiral C₂-symmetric N,N-ligands 7, which have primary aniline moieties, were readily prepared from inexpensive (R)-1,1′-binaphthol (BINOL) as a chiral source. In particular, the reaction of N-benzylidenebenzeneamine 1a with phenylacetylene 2a proceeded smoothly in the presence of 5 mol % of (CuOTf)₂·C₆H₅CH₃ and 10 mol % of (R)-7d at room temperature for 24 h, and the corresponding propargylamine 3a was obtained with up to 82% ee.     

Modiolin and phthalide derivatives from the endophytic fungus Microsphaeropsis arundinis PSU-G18

One new modiolin, microsphaerodiolin (1), and seven new phthalides, microsphaerophthalides A-G (2-8), together with 12 known compounds were isolated from the endophytic fungus Microsphaeropsis arundinis PSU-G18. Their structures were elucidated by spectroscopic methods. The new 3-oxygenated phthalides are rare natural products. The known 1-(2,5-dihydroxyphenyl)-2-buten-1-one exhibited significant antifungal activity against Microsporum gypseum SH-MU-4 with an MIC value of 8 μg/mL, moderate antimalarial activity with an IC₅₀ value of 9.63 μg/mL and strong radical scavenging potency with the IC₅₀ value of 0.018 mg/mL. The new compounds 2 and 6 showed moderately antifungal activity against M. gypseum SH-MU-4 and Cryptococcus neoformans, respectively, with equal MIC values of 64 μg/mL.     

Synthesis of (3′R,5′S)-3′-hydroxycotinine using 1,3-dipolar cycloaddition of a nitrone

To synthesize (3′R,5′S)-3′-hydroxycotinine [(+)-1], the main metabolite of nicotine (2), cycloaddition of C-(3-pyridyl)nitrones 3a, 3c, and 15 with (2R)- and (2S)-N-(acryloyl)bornane-10,2-sultam [(2R)- and (2S)-8] was examined. Among them, l-gulose-derived nitrone 15 underwent stereoselective cycloaddition with (2S)-8 to afford cycloadduct 16, which was elaborated to (+)-1.     

Syntheses,characterizations and crystal structures of monomeric or macrocyclic compounds of di- or triorganotin (IV) moieties with 4,4′-thiodibenzenethiol

Six organotin compounds with 4,4′-thiodibenzenethiol (LH₂) of the type R_nSnL_4−nSnR_n (n = 3: R = Me 1, Ph 2, PhCH₂3, n = 2: R = Me 4, Ph 5, PhCH₂6) have been synthesized. All compounds were characterized by elemental analysis, IR and NMR (¹H, ¹³C, and ¹¹⁹Sn) spectra. The structures of compounds 1, 2, 4, 5 and 6 were also determined by X-ray diffraction analysis, which revealed that compounds 1 and 2 were monomeric structures, compounds 4, 5 and 6 were centrosymmetric dinuclear macrocyclic structures, and all the tin(IV) atoms are four-coordinated. Furthermore, supramolecular structures were also found in compounds 1, 2, 4, 5 and 6, which exhibit one-dimensional chains, two-dimensional networks or three-dimensional structures through intermolecular C–H?S weak hydrogen bonds (WHBs), non-bonded Sn?S interactions or C–H?π interactions.     

2,2′-Bipyrimidine transition metal complexes: Synthesis, reaction chemistry and solid state structures

2,2′-Bipyrimidine metal complexes with Ti, Mo, Fe, Ru, Pt, Ag, and Cu transition metal atoms have been synthesized and structurally characterized. These molecules were prepared by following synthesis methodologies. The reaction of 2,2′-bipyrimidine (1; bipym) with {[Ti](μ-σ,π-CCSiMe₃)₂}AgOTf ([Ti] = (η⁵-C₅H₄SiMe₃)₂Ti, OTf = OSO₂CF₃) (2) in a 1:1 molar ratio gave [{[Ti](μ-σ,π-CCSiMe₃)₂}Ag(bipym)]OTf (3) which on further treatment with another equivalent of 2 produced [({[Ti](μ-σ,π-CCSiMe₃)₂}Ag)₂(μ-1,2,3,4-bipym)](OTf)₂ (4). As consequence thereof, the coordination number of Ag(I) was changed from 3 to 4. A platinum-bipym complex with two acetylide substituents was accessible by the gradual reaction of 1 with K₂[PtCl₄] (5) and two equivalents of HCCR (7a, R = SiMe₃; 7b, R = Fc; 7c, R = Rc; Fc = (η⁵-C₅H₄)(η⁵-C₅H₅)Fe; Rc = (η⁵-C₅H₄)(η⁵-C₅H₅)Ru) in di-iso-propylamine and in presence of [CuI]. Originating from cis-[(bipym)Pt(CCR)₂] (8a, R = SiMe₃; 8b, R = Fc; 8c, R = Rc) diverse multinuclear complexes with two, three or four different transition metals could be obtained. These are: [((CO)₄Mo)(μ-1,2,3,4-bipym)Pt(CCFc)₂] (10), [(AgClO₄)(μ-1,2,3,4-bipym){[Pt(μ-σ,π-CCFc)₂]AgOClO₃}] (12), [(McCC)₂Pt(μ-1,2,3,4-bipym)({[Ti](μ-σ,π-CCSiMe₃)₂}M)]X (15a, Mc = Fc, M = Cu, X = PF₆; 15b, Mc = Rc, M = Cu, X = PF₆; 15c, Mc = Fc, M = Ag, X = ClO₄), and [(McCC)₂Pt(μ-1,2,3,4-bipym)PtCl₂] (17). Like other organometallic Pt-Ag tweezer complexes, compound 12 decomposed to give FcCC-CCFc (13). During prolonged stirring of 15a and 15b, respectively, [(McCC)₂Pt(μ-1,2,3,4-bipym)({[Ti](μ-σ,π-CCSiMe₃)(μ-σ,π-CCH)}M)]X (15′a, M = Cu, X = PF₆; 15′b, M = Cu, X = PF₆) was formed.The structures of 8b, 8c, 15a′, and 15b′ in the solid state are reported. All complexes exhibit the anticipated planar dinuclear Pt-M structure (M = Pt, Cu, Ag) with the 2,2′-bipyrimidine unit in a μ-1,2,3,4-bridging mode.Electrochemical investigations were carried out with 8a, 8b, and 8c and show that no significant influence of R on the bipym redox potentials exists. The typical redox behavior for the bipym, ferrocene, ruthenocene units and platinum were observed.     

N-Hydroxypyridone alkaloids,chromone derivatives,and tetrahydroxanthones from the scale-insect pathogenic fungus Orbiocrella sp. BCC 33248

Six new compounds, an N-hydroxypyridone glucoside, orbiocrellin A (1), its aglycone orbiocrellin B (2), chromone glucosides 3 and 4, a dihydrochromone 5a/5b, and a chromone 6, were isolated from the scale-insect pathogenic fungus Orbiocrella sp. BCC 33248. Orbiocrellin A (1) exhibited antimalarial activity against Plasmodium falciparum K1 (IC₅₀ 3.1 μg/mL) while it was non-cytotoxic. In contrast, orbiocrellin B (2) showed both antimalarial (IC₅₀ 2.1 μg/mL) and cytotoxic (NCI-H187 cells, IC₅₀ 0.70 μg/mL) activities.     

Photoactive building blocks for coordination complexes: Gilding 2,2′:6′,2″-terpyridine

The alkyne unit of 4′-ethynyl-2,2′:6′,2″-terpyridine has been functionalized with Ph₃PAu, (2-tolyl)₃PAu or Au(dppe)Au units to produce compounds 1-3, respectively. These derivatives have been characterized by electrospray mass spectrometry, solution ¹H and ¹³C NMR, UV-Vis and emission spectroscopies, and single crystal X-ray diffraction. In the solid state, molecules of 1 or 2 pack with separated domains of tpy and R₃PAu units; the tpy units in 2 (but not 1) exhibit face-to-face π-stacking. Compound 3 crystallizes as 2(3)^.CHCl₃, and the folded conformation of the dppe backbone results in a short (2.9470(8) Å) aurophilic interaction. Folded molecule 3 captures CHCl₃, preventing intramolecular face-to-face π-interactions between the tpy units. In CH₂Cl₂ solution, 1-3 are emissive when excited between 230 and 300 nm, but over minutes when λ_ex = 230 nm, the emission bands decay as the compounds photodegrade.     

5′-Noraristeromycin possessing a C-1′ cyclopentyl double bond: a new carbanucleoside structural prototype

Prior to this work only two examples of carbanucleosides possessing a C-1′/C-6′ double bond had been reported and they were minor derivatized side products arising during other targeted syntheses. To develop this structural feature into a new class of potential antiviral agents, the 5′-nor derivative of aristeromycin with such an olefinic structure (6) represents the first example. In this regard, treatment of (1′S,2′S,3′S,4′R,5′S)-6-chloro-9-(2′,3′-isopropylidenedioxy-6′-oxabicyclo[3.1.0]hex-4′-yl)purine (7) with sodium methoxide yielded 6 via an E′₂-like elimination pathway. A convenient way to the C-4′ epimer of 6 (that is, 17) also arose during these studies and is described. Antiviral analysis of 6 and 17 failed to produce any significant activity.     

Preparation, structural characterisation and electrochemical properties of iron(0) and tungsten(0) carbonyl complexes with 1-(diphenylphosphanyl)-1′-vinylferrocene and 1-(diphenylphosphanyl)-1′-(dimethylvinylsilyl)ferrocene as P-monodentate ligands

A new organometallic phosphanylalkene, 1-(diphenylphosphanyl)-1′-(dimethylvinylsilyl)ferrocene (2) was prepared and—together with 1-(diphenylphosphanyl)-1′-vinylferrocene (1)—studied as a ligand in iron- and tungsten-carbonyl complexes. The following complexes featuring the mentioned phosphanylalkenes as P-monodentate donors were isolated and characterised by spectral methods: [Fe(CO)₄(L-κP)] (4, L = 1; 5, L = 2) and trans-[W(CO)₄(L-κP)₂] (6, L = 1; 7, L = 2). In addition, the solid-state structures of 4 and 6 have been determined by single-crystal X-ray diffraction and the electrochemical properties of compounds 1, 2, 4 and 6 were studied by cyclic voltammetry at platinum electrode.     

Titanium (IV) complexes based on substituted 2-[(2-hydroxyethyl)]aminophenols

Novel substituted 2-[(2-hydroxyethyl)]aminophenols, MeN(CHR¹CR²R³OH)(C₆H₄-o-OH) (2-5), were synthesized by the reaction of 2-methylaminophenol with corresponding oxiranes. Titano-spiro-bis(ocanes) [MeN(CHR¹CR²R³O)(C₆H₄-o-O)]₂Ti 6-9 (2, 6, R¹ = H, R² = R³ = Me; 3, 7, R¹ = R² = Ph (treo-), R³ = H; 4, 8, R¹ = Ph, R² = R³ = H; 5, 9, R¹ = R² = H, R³ = Ph) based on [ONO]-ligands have been synthesized. The obtained compounds were characterized by ¹H and ¹³C NMR spectroscopy and elemental analysis data. The complex [Ti(μ²-O){O-o-C₆H₄}{μ²-CMe₂CH₂}NMe]₆ (10) was obtained by controlled hydrolysis of 6. Molecular structure of 10 was determined by X-ray structure analysis.     

Photocytotoxic and anaerobic DNA cleavage activity of binuclear 3,3′-dithiodipropionic acid cobalt(II) complexes having phenanthroline bases

Dicobalt(II) complexes [{(B)Co^II}₂(μ-dtdp)₂] (1–3) of 3,3′-dithiodipropionic acid (dtdp) and phenanthroline bases (B), viz. 1,10-phenanthroline (phen in 1), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq in 2) and dipyrido[3,2-a:2′,3′-c]phenazine (dppz in 3), have been prepared, characterized and their photo-induced anaerobic DNA cleavage activity studied. The elemental analysis and mass spectral data suggest binuclear formulation of the complexes. The redox inactive complexes have magnetically non-interacting dicobalt(II) core showing magnetic moment of ∼3.9 μ_B per cobalt(II) center. The complexes show good binding propensity to calf thymus DNA giving K_b values within 4.3 × 10⁵–4.0 × 10⁶ M⁻¹. Thermal melting and viscosity data predict DNA groove binding and/or partial intercalative nature of the complexes. The complexes show significant anaerobic DNA cleavage activity in green light under argon atmosphere possibly involving radical species generated from the disulfide moiety in a type-I pathway. The DNA cleavage reaction under aerobic medium in green light is found to involve hydroxyl radical species. The dppz complex 3 exhibits significant photocytotoxicity in HeLa cervical cancer cells with an IC₅₀ value of 2.3 μM in UV-A light of 365 nm, while it is essentially non-toxic in dark giving an IC₅₀ value of >200 μM. A significant reduction of the dark toxicity of the organic dppz base (IC₅₀ = 8.3 μM in dark) is observed on binding to the cobalt(II) center while essentially retaining its photocytotoxicity in UV-A light (IC₅₀ = 0.4 μM).     

Crystallization-based optical resolution of 1,1′-binaphthalene-2,2′-dicarboxylic acid via 1-phenylethylamides: control by the molecular structure and dielectric property of solvent

In the recrystallization of a diastereomeric mixture of amides (RS_a,S)-1 formed from racemic 1,1′-binaphthalene-2,2′-dicarboxylic acid and (S)-1-phenylethylamine, either of the diastereomers crystallizes out as a diastereomerically pure form, depending on the solvent employed; sterically undemanding solvents, acetone, dichloromethane, and acetonitrile, afford crystals formulated as (S_a,S)-1·solvent with an exception of ethanol, which affords (R_a,S)-1·EtOH, while sterically bulkier solvents afford (R_a,S)-1 including no solvent. The stereoselectivity can be rationalized by the crystal structures. A dielectrically controlled resolution (DCR) can also be carried out by using mixed solvents, which contain, for example, 25 vol % of acetone and varying ratios of hexane and 1-propanol in total 75 vol %; (S_a,S)-1·acetone is deposited as crystals from the solvents with a dielectric constant (ε) range 8.9 ? ε ? 10.2, while (R_a,S)-1 is deposited from the solvents with 14.8 ? ε ? 20.3.     

Absolute configuration and antibiotic activity of neosartorin from the endophytic fungus Aspergillus fumigatiaffinis

Neosartorin (1) was isolated from the endophytic fungus Aspergillus fumigatiaffinis. The absolute configuration of 1, including both axial and central chirality elements, was established as (aR,5S,10R,5′S,6′S,10′R) for the first time on the basis of its electronic circular dichroism (ECD) spectra aided with TDDFT–ECD calculations. Neosartorin (1) exhibited substantial antibacterial activity against a broad spectrum of Gram-positive bacterial species including staphylococci, streptococci, enterococci, and Bacillus subtilis with minimal inhibitory concentrations in the range of 4–32 μg/mL. When the toxicity of 1 against eukaryotic cells was measured using a panel of different cancer cell lines such as HELA and BALB/3T3, the average IC₅₀ values exceeded 32 μg/mL.     

Polyketides from the mangrove-derived endophytic fungus Acremonium strictum

Five new polyketide derivatives, 6′-hydroxypestalotiopsone C (1), acropyrone (2), bicytosporone D (3), waol acid (4), and pestalotiopene C (5), together with seven known metabolites (6–12), were obtained from extracts of the endophytic fungus Acremonium strictum, isolated from the mangrove tree Rhizophora apiculata. The structures of the isolated compounds were elucidated on the basis of comprehensive NMR and MS analysis. Compounds 6, 7, and 9 showed moderate cytotoxic activity against human cisplatin-sensitive (IC₅₀ values 27.1, 76.2, and 8.3 μM, respectively) and resistant A2780 cell lines (IC₅₀ values 12.6, 30.1, and 19.0 μM, respectively), whereas only 9 exhibited antibacterial activity against Staphylococcus aureus (MIC value 14.3 μM).     

A convenient synthesis of substituted 2,2′:6′,2″-terpyridines

The 2,2′:6′,2″-terpyridines 8a and 8b were prepared in good yield by reacting α-acetoxy-α-chloro-β-keto-esters 1 (R¹ = ⁿPr and Ph) with the bis-amidrazone 7 and 2,5-norbornadiene 5 in ethanol at reflux.     

Constituents of the Leaves and Stem Bark of Aglaia foveolata

The previously known potent cytotoxic agent silvestrol (1) (0.002% w/w yield) and five new flavagline derivatives (2-6) were isolated from the leaves of Aglaia foveolata collected in Indonesia. The new compound 5 has an unprecedented cyclic amide moiety in its cyclopenta[b]benzopyran skeleton, while compound 6 is a novel benzo[b]oxepine derivative in which the oxepine ring is cleaved. Pyramidatine (7), a biogenetic precursor of the new flavaglines 2-6, was isolated from the leaf extract investigated. Silvestrol was also isolated from the stem bark of A. foveolata (yield of 0.02% w/w) along with a new baccharane-type triterpenoid (8). The structures of the new compounds were elucidated on the basis of their NMR and mass spectrometric data. All new compounds isolated were tested against a panel of cancer cell lines, but only compound 2 was cytotoxic (IC₅₀ range=1.4-1.8 μM), and is the first member of the cyclopenta[b]benzopyran class found to exhibit this type of activity. Compound 2 also showed significant NF-κB inhibitory activity in an Elisa assay (IC₅₀=0.37 μM).     

Electronically variable imino-phenanthrolinyl-cobalt complexes; synthesis, structures and ethylene oligomerisation studies

The 2-imino-1,10-phenanthroline ligands, 1,10-C₁₂H₇N₂-2-CRN(2,6-i-Pr₂-4-R¹-C₆H₂) [R = R¹ = H (L1); R = H, R¹ = Br (L2); R = H, R¹ = CN (L3); R = H, R¹ = i-Pr (L4); R = Me, R¹ = H (L5); R = Me, R¹ = i-Pr (L6)], have been prepared in high yield from the condensation reaction of 1,10-C₁₂H₇N₂-2-CRO (R = H, Me) with one equivalent of the corresponding 4-substituted 2,6-diisopropylaniline. The molecular structures of L2, L5 and L6 reveal the imino nitrogen atoms to adopt a transoid configuration with respect to the phenanthrolinyl nitrogen atoms. Treatment of Lx with one equivalent of CoCl₂ in n-BuOH at 90 °C gives the high spin complexes, (Lx)CoCl₂ [Lx = L1 (1a), L2 (1b), L3 (1c), L4 (1d), L5 (1e), L6 (1f)], in which the metal centres exhibit distorted square pyramidal geometries. Activation of 1a-1f with excess methylaluminoxane (MAO) gives catalysts that are modestly active for the oligomerisation of ethylene affording mainly linear α-olefins along with some degree of internal olefins. While the donor capability of the 4-position of the N-aryl group does not appear to affect the activity of the catalyst, it does have an influence on the ratio of α-olefins to internal olefins. Single crystal X-ray diffraction studies have been performed on L2, L5, L6, 1a, 1c and 1f.     

Synthesis,structure and reactivity of novel palladiumdichloride-2,2′-bipyridine with 4,4′-bis(fluorous-ponytail)

With the readily available fluorous alkanols R_fCH₂OH, a series of novel fluorous-ponytailed bpy ligands, 4,4′-bis(R_fCH₂OCH₂)-2,2′-bpy (1a–e), were prepared and treated with [PdCl₂(CH₃CN)₂] to result in the corresponding novel Pd complexes [PdCl₂(4,4′-bis(R_fCH₂OCH₂)-2,2′-bpy)] (2a–e) where R_f = n-C₃F₇ (a), HCF₂(CF₂)₃ (b), HCF₂(CF₂)₇ (c), n-C₈F₁₇ (d), n-C₁₀F₂₁ (e). The new ligands and Pd complexes were spectroscopically characterized by multi-nuclei NMR (¹H, ¹⁹F and ¹³C), FTIR and high resolution mass (FAB). The structure for the Pd complex 2b, the first with fluorinated ponytails on bpy and not on phosphine, was also established by a single crystal X-ray diffraction study. The TGA data of both ligands and Pd complexes indicated that the Pd-complexes were resistant to higher temperatures than the corresponding ligands. The Pd catalysts derived from 2a–c showed an almost quantitative conversion and could be reused for eight runs with Heck reactions, in that the products and unspent reactants were directly removed by distillation. With the highest fluorine content in the series, Pd complex 2e was successfully applied in the Heck reaction using the fluorous biphasic catalysis strategy.     

Fe Spin crossover materials based on dissymmetrical N4 Schiff bases including 2-pyridyl and 2R-imidazol-4-yl rings: Synthesis,crystal structure and magnetic and Mössbauer properties

The synthesis and characterization of new symmetrical Fe^II complexes, [FeL^A(NCS)₂] (1), and [FeL^Bx(NCS)₂] (2–4), are reported (L^A is the tetradentate Schiff base N,N′-bis(1-pyridin-2-ylethylidene)-2,2-dimethylpropane-1,3-diamine, and L^Bx stands for the family of tetradentate Schiff bases N,N′-bis[(2-R-1H-imidazol-4-yl)methylene]-2,2-dimethylpropane-1,3-diamine, with: R = H for L^B1 in 2, R = Me for L^B2 in 3, and R = Ph for L^B3 in 4). Single-crystal X-ray structures have been determined for 1 (low-spin state at 293 K), 2 (high-spin (HS) state at 200 K), and 3 (HS state at 180 K). These complexes remain in the same spin-state over the whole temperature range [80–400 K]. The dissymmetrical tetradentate Schiff base ligands L^Cx, N-[(2-R₂-1H-imidazol-4-yl)methylene]-N′-(1-pyridin-2-ylethylidene)-2,2-R₁-propane-1,3-diamine (R₁ = H, Me; R₂ = H, Me, Ph), containing both pyridine and imidazole rings were obtained as their [FeL^Cx(NCS)₂] complexes, 5–10, through reaction of the isolated aminal type ligands 2-methyl-2-pyridin-2-ylhexahydropyrimidine (R₁ = H, 5–7) or 2,5,5-trimethyl-2-pyridin-2-ylhexahydropyrimidine (R₁ = Me, 8–10) with imidazole-4-carboxaldehyde (R₂ = H: 5, 8), 2-methylimidazole-4-carboxaldehyde (R₂ = Me: 6, 9), and 2-phenyl-imidazole-4-carboxaldehyde (R₂ = Ph: 7, 10) in the presence of iron(II) thiocyanate. Together with the single-crystal X-ray structures of 7 and 9, variable-temperature magnetic susceptibility and Mössbauer studies of 5–10 showed that it is possible to tune the spin crossover properties in the [FeL^Cx(NCS)₂] series by changing the 2-imidazole and/or C2-propylene susbtituent of L^Cx.