Chemistry of renieramycins. Part 7: Renieramycins T and U, novel renieramycin-ecteinascidin hybrid marine natural products from Thai sponge Xestospongia sp.

Two new bistetrahydroisoquinoline marine natural products, renieramycins T (1) and U (2), were isolated from the Thai blue sponge Xestospongia sp. and their structures were elucidated by comparing spectral data with those of renieramycin M (3a) and ecteinascidin 770 (4a). These compounds are the first reported examples of novel ecteinascidin-renieramycin hybrid natural products. Renieramycin T (1) showed strong cytotoxicity to several human cancer cell lines, its IC₅₀ values ranging from 4.7 to 98 nM.     

Vinyl-addition polymerization of norbornene catalyzed by (pyrazol-1-ylmethyl)pyridine divalent iron, cobalt and nickel complexes

Complexes of 2-((3,5-dimethyl)-1H-pyrazol-1-ylmethyl)pyridine (L1), 2-((3,5-ditert-butyl-1H-pyrazol-1-yl)methyl)pyridine (L2), 2-((3,5-diphenyl)-1H-pyrazol-1-yl)methyl)pyridine (L3), 2-((3,5-bis(trifluoromethyl)-1H-pyrazol-1-ylmethyl)pyridine (L4) and 2,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)methyl)pyridine (L5) with cobalt(II), iron(II) and nickel(II), Ni(L1)Cl₂ (1), Co(L1)Cl₂ (2), Fe(L1)Cl₂ (3), Ni(L2)Cl₂ (4), Ni(L3)Cl₂ (5), Co(L3)Cl₂ (6), Fe(L3)Cl₂ (7), Ni(L4)Cl₂ (8) and Ni(L5)Cl₂ (9), were used as catalyst precursors to produce vinyl-addition type norbornene polymers. Both the identity of the metal center and nature of ligand affected the polymerization behaviour of the resultant catalysts. Nickel catalysts were generally more active than the corresponding iron and cobalt analogues. The polynorbornene produced have high molecular weights (0.5-2.1 × 10⁶ g/mol) and narrow molecular weight distributions. Analyses of polymer microstructure using NMR and IR spectroscopy confirmed the polymers produced to be vinyl-addition polynorbornene.     

Pyrazolyl iron, cobalt, nickel, and palladium complexes: synthesis, molecular structures, and evaluation as ethylene oligomerization catalysts

Reactions of [2-(3,5-dimethyl-pyrazol-1-yl)-ethanol] (L1) and [1-(2-chloro-ethyl)-3,5-dimethyl-1H-pyrazole] (L2) with Fe(II), Co(II), Ni(II), and Pd(II) salts gave the complexes [(L1)₂FeCl₂] (1), [(L1)₂CoCl₂] (2), [(L1)₂NiBr₂] (3), [(L1)₂Pd(Me)Cl] (5), [(L2)₂CoCl₂] (6), and [(L2)₂NiBr₂] (7). Whereas L2 behaves as a monodentate ligand, L1 can behave as either a monodentate or bidentate ligand depending on the nature of the metal centre. For palladium, L1 is monodentate in the solid state structure of 5 but bidentate in the structure of 4, obtained during attempts to crystallize 3. While the activation of iron, cobalt and palladium complexes with EtAlCl₂ did not produce active ethylene oligomerization catalysts, the nickel complexes 3 and 7 produced active ethylene oligomerization catalysts. Activities as high as 4329 kg/mol Ni h were obtained. Catalyst 3 produced mainly butenes (57%) and hexenes (43%); of which a combined 20% were converted to Friedel-Crafts alkylated-toluene. Catalyst 7, on other hand, produced mainly butenes (90%) and small amounts of hexenes (10%) which were then completely converted to the corresponding Friedel-Crafts alkylated-toluene products. This difference in product distribution in catalysis performed by complexes 3 and 7 is indicative of the role of the OH functionality in L1 on the EtAlCl₂ co-catalysts.     

New phlegmarane-type, cernuane-type, and quinolizidine alkaloids from two species of Lycopodium

Two new phlegmarane-type alkaloids, cermizines A (1) and B (2), three new quinolizidine alkaloids, cermizine C (3) and senepodines G (4) and H (5), and a new C₁₆N₂ type alkaloid consisting of a quinolizidine and a piperidine ring, cermizine D (6), as well as two new cernuane-type alkaloids, cernuine N-oxide (7) and lycocernuine N-oxide (8), have been isolated together with cernuine (9) and lycocernuine (10) from the club moss Lycopodium cernuum and L. chinense. The relative stereochemistry of 1-4 and 6, and the absolute stereochemistry of 5, 7, and 8 were elucidated by combination of NOESY correlations, modified Mosher's method, chemical transformations, and computational methods. Cermizine D (6) might be a biosynthetic intermediate of cernuane-type alkaloids such as 7-10.     

Cytotoxic dimeric sesquiterpenoids from Curcuma parviflora: isolation of three new parviflorenes and absolute stereochemistry of parviflorenes A, B, D, F, and G

Three novel dimeric sesquiterpenoids, named parviflorenes G-I (1-3), have been isolated from Curcuma parviflora (Zingiberaceae), and their structures were elucidated by means of spectroscopic studies. Absolute stereochemistry of parviflorene G (1) as well as previously isolated related compounds, parviflorenes A (4), B (5), D (6), and F (7), was revealed by CD spectral data and chemical means. Parviflorenes G (1) and I (3) were cytotoxic against HeLa cells, while parviflorenes A (4) and F (7) were cytotoxic against all tested tumor cell lines in the human cancer cell line panel assay.     

Synthesis, photophysical and photochemical properties of highly soluble phthalocyanines substituted with four 3,5-dimethylpyrazole-1-methoxy groups

The synthesis and characterization of new peripherally tetra-3,5-dimethylpyrazole-1-methoxy substituted metal-free (4), zinc (5), nickel (6), cobalt (7), copper (8) and lead (9) phthalocyanines are described for the first time in this study. The photophysical (fluorescence quantum yields and fluorescence lifetimes) and photochemical (photodegradation and singlet oxygen quantum yields) properties of metal-free (4), zinc (5) and lead (9) phthalocyanines are studied in dimethylsulfoxide (DMSO). Nickel (6), cobalt (7) and copper (8) phthalocyanines (6-8) did not evaluate for this purpose due to transition metal and paramagnetic behavior of central metals in the phthalocyanine cavity. The fluorescence quenching behavior of metal-free (4), zinc (5) and lead (9) phthalocyanines are also investigated. The fluorescence emissions of these phthalocyanines are effectively quenched by 1,4-benzoquinone in DMSO.     

Structural and stereochemical investigations into bromotyrosine-derived metabolites from southern Australian marine sponges, Pseudoceratina spp.

Chemical investigation of a southern Australian sponge, Pseudoceratina sp., resulted in the isolation of twelve bromotyrosine-derived alkaloids, comprising four new metabolites, aplysamine-7 (1), (−)-purealin B (2), purealin C (3) and purealin D (4); two new spiroisoxazole enantiomers, (−)-purealidin R (5) and (−)-aerophobin-2 (6); five known metabolites (−)-pseudoceratinine A (7), (−)-aeroplysinin-1 (8), aplysamine-2 (9), purpuramine G (10) and purpuramine J (11); and an artifact 12 derived from ethanolysis of 5. Structures for 1-12 were assigned on the basis of detailed spectroscopic analysis. A second southern Australian Pseudoceratina sp. afforded the first recorded account of a racemic bromotyrosine-derived spiroisoxazole, (±)-purealin (13b), together with the known achiral precursor purealidin A (15). A literature review of marine bromotyrosine-derived spiroisoxazoles reaffirmed the published dominance of (+)-spiroisoxazoles, acknowledging several accounts of (−)-spiroisoxazoles, while also revealing a wide range of chiroptical measurements suggestive of variable optical purity. The Pseudoceratina sp. metabolites 1-12, 13b and 15 were assessed for antibiotic properties, with the new metabolites 3 and 13b exhibiting broad spectrum activity against several Gram-positive bacteria.     

Synthesis of 12-deoxyroyleanone, cryptoquinone, 11,14-dihydroxy-8,11,13-abietatrien-7-one, and related derivatives from dehydroabietic acid

Naturally occurring abietane quinones and hydroquinone, namely, 12-deoxyroyleanone (1a), cryptoquinone (4a), and 11,14-dihydroxyabieta-8,11,13-trien-7-one (5a), together with the epimers of tryptoquinones D (2) and F (3), were first synthesized from dehydroabietic acid (6).     

Structure,biological and electrochemical studies of transition metal complexes from N,S,N′ donor ligand 8-(2-pyridinylmethylthio)quinoline

The semirigid tridentate 8-(2-pyridinylmethylthio)quinoline ligand (Q1) is shown to form the structurally characterized transition metal complexes [Cu(Q1)Cl₂] (1), [Co(Q1)(NO₃)₂] (2), [Cd(Q1)(NO₃)₂] (3), [Cd(Q1)I₂] (4). [Cu(Q1)₂](BF₄)₂·(H₂O)₂ (5), [Cu(Q1)₂](ClO₄)₂·(CH₃COCH₃)₂ (6), [Zn(Q1)₂](ClO₄)₂(H₂O)₂ (7), [Cd₂(Q1)₂Br₄] (8), [Ag₂(Q1)₂(ClO₄)₂] (9), and [Ag₂(Q1)₂(NO₃)₂] (10). Four types of structures have been observed: ML-type in complexes 1–4, in which the anions Cl⁻, NO₃⁻ or I⁻ also participate in the coordination; ML₂⁻ type in complexes 5–7 without direct coordination of the anions BF₄⁻ or ClO₄⁻ and with more (Cu²⁺) or less (Zn²⁺) distorted bis-fac coordinated Q1; M₂L₂-type in complex 8, in which two Br⁻ ions act as bridges between two metal ions; and M₂(μ-L)₂-type in complexes 9 and 10, in which the ligand bridges two anion binding and Ag–Ag bonded ions. Depending on electron configuration and size, different coordination patterns are observed with the bonds from the metal ions to N_pyridyl longer or shorter than those to N_quinoline. Typically Q1 acts as a facially coordinating tridentate chelate ligand except for the compounds 9 and 10 with low-coordinate silver(I). Except for 6 and 8, the complexes exhibit distinct constraining effects against both G(+) and G(-) bacteria. Complexes 1, 3, 4, 5, 7 have considerable antifungal activities and complexes 1, 5, 7, and 10 show selective effects to restrain certain botanic bacteria. Electrochemical studies show quasi-reversible reduction behavior for the copper(II) complexes 1, 5 and 6.     

Daphniglaucins D-H, J, and K, new alkaloids from Daphniphyllum glaucescens

Five new fused-hexacyclic alkaloids, daphniglaucins D (1), E (2), F (3), G (4), and H (5), and two new yuzurimine-type alkaloids, daphniglaucins J (6) and K (7), have been isolated from the leaves of Daphniphyllum glaucescens, and the structures and relative stereochemistry were elucidated on the basis of spectroscopic data and chemical means.     

The high-temperature alicyclic ring contraction of 1,1-dichloroperfluorotetralin and the alicyclic ring opening of 1,1-dichloroperfluorobenzocyclobutene

The pyrolysis of 1,1-dichloroperfluorotetralin (4) in a stream of argon gives a mixture contained perfluoro-1-methyleneindan (1), perfluoro-3-methylindene (6), 1,1-dichloroperfluoroindan (2) and perfluoroindene (7), while copyrolysis of tetralin 4 with CHClF₂ gives a mixture of compounds 1, 6 in the absence of compounds 2 and 7. 1-Chloro-2-(1-chloro-2,2-difluorovinyl)-3,4,5,6-tetrafluorobenzene (12) is formed in the pyrolysis of 1,1-dichloroperfluorobenzocyclobutene (5) in a stream of argon as well as in a stream of CHClF₂.     

Zn-promoted regio- and sequence-selective one-pot joining reactions of three components: vinylpyridines, alkyl iodides, and carbonyl compounds (or nitriles)

Addition of alkyl iodides (3) into the solution containing 2-(or 4-)vinylpyridine (1 or 2) and carbonyl compounds (6) in the presence of Zn-powder (99.9%) in acetonitrile under refluxing brought about regio- and sequence-selective joining reaction of three components to give the corresponding (2-hydroxyethyl)pyridines (7 or 8) in good to moderate yields. On the other hand, 2-(2- or 4-pyridyl)ethyl alkyl ketones (10 or 11) were obtained from the similar joining reaction of three components by addition of alkyl iodides (3) into the solution of 2-(or 4-)vinylpyridine (1 or 2), and nitriles (9) in toluene containing Zn-powder (99.9%) under the similar reaction conditions.     

Synthesis, characterization and spectroscopic studies of cyclometalated platinum(II) complexes containing meta-bis(2-pyridoxy)benzene

A series of mononuclear and binuclear cyclometalated platinum(II) complexes containing new terdentate meta-bis(2-pyridoxy)benzene ligands: 3,5-bis(2-pyridoxy)toluene (L₁H) and 3,5-bis(2-pyridoxy)-2-dodecylbenzene (L₂H): [Pt(L₁)Cl] (1), [Pt(L₂)Cl] (2), [Pt(L₁)(CH₃CN)](ClO₄) (3), {[Pt(L₁)]₂(μ-dppm)}(ClO₄)₂ (4), {[Pt(L₂)]₂(μ-dppm)}(ClO₄)₂ (5), {[Pt(L₁)]₂(μ-pyrazole)}(ClO₄) (6), {[Pt(L₂)]₂(μ-pyrazole)}(ClO₄) (7), {[Pt(L₁)]₂(μ-imidazole)}(ClO₄) (8) and {[Pt(L₂)]₂(μ-imidazole)}(ClO₄) (9), have been synthesized and characterized. These ligands are coordinated to platinum(II) in a “pincer”-like manner and the presence of pyridyl donors enhances the availability of the ligand π^∗ orbitals for electronic transition. Spectroscopic properties of these cyclometalated complexes were studied. While the non-coplanar nature of the ligands hinders ligand-ligand and metal-metal interactions in these cyclometalated complexes, the presence of long hydrocarbon side chain on ligand L₂H seems to alleviate such hindrance. Intermolecular π-π, and possibly Pt-Pt interactions were observed in complex 2 at high concentration.     

A contribution to 1-azapentadienylmetal chemistry: Si, Sn(II), Fe(II) and Co(II) complexes

Complexes of three related 1-azapentadienyl ligands [N(SiMe₂R¹)C(Bu^t)(CH)₃SiMe₂R]⁻, abbreviated as L (R = Bu^t, R¹ = Me), L′ (R = Me = R¹), and L″ (R = Bu^t = R¹), are described. The crystalline compounds Sn(L)₂ (1), Sn(L′)₂ (2), [Sn(L′)(μ-Cl)]₂ (3) and [Sn(L″)(μ-Cl)]₂ (4) were prepared from SnCl₂ and 2 K(L), 2 K(L′), K(L′) and K(L″), respectively, in thf. Treatment of the appropriate lithium 1-azapentadienyl with Si(Cl)Me₃ yielded the yellow crystalline Me₃Si(L) (5) and the volatile liquid Me₃Si(L′) (6) and Me₃Si(L″) (7), each being an N,N,C-trisilyldieneamine. The red, crystalline Fe(L)₂ (8) and Co(L′)₂ (9) were obtained from thf solutions of FeCl₂ with 2 Li(L)(tmeda) and CoCl₂ with 2 K(L′), respectively. Each of 1-9 gave satisfactory C, H, N analyses; 6 and 7 (GC-MS) and 1, 2, 8 and 9 (MS) showed molecular cations and appropriate fragments (also 3 and 4). The ¹H, ¹³C and ¹¹⁹Sn NMR (1-4) and IR spectra support the assignment of 1-4 as containing Sn-N(SiMe₂R¹)-C(Bu^t)(CH)₃SiMe₂R moieties and 5-7 as N(SiMe₃)(SiMe₂R¹)C(Bu^t)(CH)₃SiMe₂R molecules; for 1-4 this is confirmed by their X-ray structures. The magnetic moments for 8 (5.56 μ_B) and 9 (2.75 μ_B) are remarkably close to the appropriate Fe and Co complex [M{η³-N(SiMe₃)C(Bu^t)C(H)SiMe₃}₂]; hence it is proposed that 8 and 9 have similar metal-centred, centrosymmetric, distorted octahedral structures.     

Cortistatins J, K, L, novel abeo-9(10-19)-androstane-type steroidal alkaloids with isoquinoline unit, from marine sponge Corticium simplex

Three novel anti-angiogenic steroidal alkaloids, cortistatins J (1), K (2), L (3), have been isolated from the Indonesian marine sponge Corticium simplex. The chemical structures of cortistatins J (1), K (2), and L (3) were determined by 2D-NMR analysis to be unique abeo-9(10-19)-androstane-type steroidal alkaloids having isoquinoline unit instead of the side chain part, respectively. Cortistatin J (1) showed cytostatic anti-proliferative activity against human umbilical vein endothelial cells (HUVECs) at 8 nM, in which the selective index was 300-1000-fold in comparison with other cell lines.     

Chemically modified oximato complexes of titanium(IV) isopropoxide as new precursors for the sol-gel preparation of nano-sized titania: Crystal and molecular structure of [Ti{ONC10H16}4·2CH2Cl2]

Reactions of [Ti(OPrⁱ)₄] with various oximes, in anhydrous refluxing benzene yielded complexes of the type [Ti{OPrⁱ}_4−n{L}_n], where, n = 1-4 and LH = (CH₃)₂CNOH (1-4), C₉H₁₆CNOH (5-8) and C₉H₁₈CNOH (9-12). The compounds were characterized by elemental analyses, molecular weight measurements, FAB-mass, FT-IR and NMR (¹H, ¹³C{¹H}) spectral studies. The FAB-mass spectra of mono- (1), and di- (2), (6), (10) substituted products indicate their dimeric nature and that of tri- (3) and tetra- (4), (8) substituted derivatives suggest their monomeric nature. Crystal and molecular structure of [Ti{ONC₁₀H₁₆}₄·2CH₂Cl₂] (8A) suggests that the oximato ligands bind the metal in a dihapto η²-(N, O) manner, leading to the formation of an eight coordinated species. Thermogravimetric curves of (3), (6) and (10) exhibit multi-step decomposition with the formation of TiO₂ as the final product in each case, at 900 °C. Low temperature (∼600 °C) sol-gel transformations of (2), (3), (4), (6), (7) and (8) yielded nano-sized titania (a), (b), (c), (d), (e) and (f), respectively. Formation of anatase phase in all the titania samples was confirmed by powder XRD patterns, FT-IR and Raman spectroscopy. SEM images of (a), (b), (c), (d), (e) and (f) exhibit formation of nano-grains with agglomer like surface morphologies. Compositions of all the titania samples were investigated by EDX analyses. The absorption spectra of the two representative samples, (a) and (f) indicate an energy band gap of 3.17 eV and 3.75 eV, respectively.     

Isolation, structure elucidation and bioactivity of schischkiniin, a unique indole alkaloid from the seeds of Centaurea schischkinii

Reversed-phase HPLC analysis of the methanol extract of the seeds of Centaurea schischkinii afforded a novel indole alkaloid, named schischkiniin (1), together with four lignans, arctiin (2), matairesinoside (3), matairesinol (4), and arctigenin (5), and three flavonoids, astragalin (6), afzelin (7) and apigenin (8). While the structure of schiskiniin (1) was established unequivocally by UV, HRFABMS and a series of 1D and 2D NMR analyses, all known compounds were readily identified by comparison of their spectroscopic data with literature data. The free radical scavenging properties of these compounds were assessed using the DPPH assay, and their general toxicity and cytotoxicity were evaluated, respectively, by brine shrimp lethality and MTT cytotoxicity assays with CaCo-2 colon cancer cell lines. Arctigenin (5) exhibited promising in vitro anticancer activity (IC₅₀=7 μM) while with schischkiniin (1) the activity was of moderate level (IC₅₀=76 μM).     

Syntheses,crystal structures,and magnetic and luminescent properties of a series of lanthanide coordination polymers with chelidamic acid ligand

A series of lanthanide(III) complexes with chelidamic acid ligand, [Ln(C₇H₂NO₅)·3H₂O]_n·nH₂O (Ln = La (1), Y (2), Sm (3), and Nd (4)), [Gd₂(C₇H₂NO₅)₃·4H₂O]_n·2nH₂O (5) and [Ce(C₇H₂NO₅)·1.5H₂O]_n (6), have been synthesized by hydrothermal method and structurally characterized by single-crystal X-ray diffraction. Complexes 1–4 are isostructural and possess 2D framework. Complex 5 contains two different Gd(III) ions linked through carboxylate group to form a 2D framework. Complex 6 exhibits a (4⁴) topology 2D network. The variable-temperature magnetic properties of 3 and 5 have been investigated. Furthermore, the photoluminescent properties of 1, 2, 3, and 5 at room temperature were also studied.     

The first sorbicillinoid alkaloids, the antileukemic sorbicillactones A and B, from a sponge-derived Penicillium chrysogenum strain

The saltwater culture of a Penicillium chrysogenum strain isolated from the Mediterranean sponge Ircinia fasciculata yielded three new sorbicillin-derived compounds (1-3), whose structures were elucidated mainly by 2D NMR and mass spectrometry. Among them, sorbicillactones A (1) and B (2) are the first sorbicillinoid natural products that contain nitrogen. Compound 1 is anti-HIV active and it exhibits a strong cytotoxic activity against L5178y leukemic cells, combined with a relatively low toxicity to cervical carcinoma HeLa S3 cells and pheochromocytoma PC 12 cells. The absolute configurations of 1 and 2 were elucidated by quantum chemical calculation of circular dichroism (CD) spectra. Another compound isolated, sorbivinetone (3), might be an artifact derived from sorbicillinol (4) by Diels-Alder reaction with ethyl vinyl ether. Furthermore, the known sorbicillinoid fungal metabolites oxosorbicillinol (5), sorbicillin (6), and bisvertinolone (7) were identified, as well as the alkaloids meleagrine and roquefortine C. The biosynthetic origin of sorbicillactone A (1) from acetate, alanine, and methionine was investigated by feeding experiments with ¹³C-labeled precursors.     

Synthesis,structural analysis,and thermal and spectroscopic studies of methylmalonate-containing zinc(II) complexes

The synthesis, crystal structure, thermal analysis and spectroscopic studies of five zinc(II) complexes of formulae [Zn(Memal)(H₂O)]_n (1) and [Zn₂(L)(Memal)₂(H₂O)₂]_n (2-5) [H₂Memal = methylmalonic acid, and L = 4,4′-bipyridine (4,4′-bpy) (2), 1,2-bis(4-pyridyl)ethylene (bpe) (3), 1,2-bis(4-pyridyl)ethane (bpa) (4) and 4,4′-azobispyridine (azpy) (5)] are presented here. The crystal structure of 1 is a three-dimensional arrangement of zinc(II) cations interconnected by methylmalonate groups adopting the μ₃-κ²O:κO’:κO”:κO”’ coordination mode to afford a rare (10,3)-d utp-network. The structures of the compounds 2-5 are also three-dimensional and they consist of corrugated square layers of methylmalonate-bridged zinc(II) ions which are pillared by bis-monodentate 4,4′-bpy (2), bpe (3), bpa (4) and azpy (5) ligands. The Memal ligand in 2-5 adopts the μ₃-κO:κO′:κO′′:κO′′′ coordination mode. Each zinc(II) ion in 1-5 is six-coordinated with five (1)/four (2-5) methylmalonate-oxygen atoms, a water molecule (1-5) and a nitrogen atom from a L ligand (2-5) building distorted octahedral environments. The rod-like L co-ligands in 2-5 appear as useful tools to control the interlayer metal-metal separation, which covers the range 8.4311(5) Å (2) – 9.644(3) Å (5). The influence of the co-ligand on the fluorescence properties of this series of compounds has been analyzed and discussed by steady-state and time resolved spectroscopy on all five compounds in the solid state.