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Liva Harinantenaina,
Jessica D Bowman,
Peggy J Brodie, Carla Slebodnick,
Martin W Callmander,
Etienne Rakotobe,
Richard Randrianaivo,
Vincent E Rasamison,
Alexander Gorka,
Paul D Roepe,
Maria B Cassera,
David G I Kingston
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ABSTRACT: Bioassay-guided fractionation of an ethanol extract of the leaves and inflorescence of Mallotus oppositifolius collected in Madagascar led to the isolation of the two new bioactive dimeric phloroglucinols mallotojaponins B (1) and C (2), together with the known mallotophenone (3). The structures of the new compounds were determined on the basis of spectroscopic evidence, including their 1D- and 2D-NMR spectra, mass spectrometry, and an X-ray crystal structure. Compounds 1 and 2 showed potent antimalarial activity against chloroquine-resistant Plasmodium falciparum, with IC(50) values of 0.75 ± 0.30 and 0.14 ± 0.04 μM, while 3 was inactive in this assay. Compounds 1-3 also displayed strong antiproliferative activity against the A2780 human ovarian cancer cell line (IC(50) 1.10 ± 0.05, 1.3 ± 0.1 and 6.3 ± 0.4 μM, respectively).
Journal of Natural Products 01/2013; · 3.13 Impact Factor
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ABSTRACT: A new cryptand/paraquat [2]pseudorotaxane and its crown ether analog were synthesized and characterized by proton NMR, mass
spectrometry, and single crystal X-ray analysis. The Job plots based on proton NMR data demonstrated that both the complex
between cryptand 1 and paraquat derivative 2a and the complex between bis(p-phenylene)-34-crown-10 (3) and paraquat derivative 2b have 1:1 stoichiometry in solution. The apparent association constants (K
a,exp) of 1·2a and 3·2b calculated for 1:1 complexes were 1.4 (±0.2) × 104 and 4.7 (±0.5) × 102 M−1, respectively. X-ray analysis showed that 1·2a is stabilized by ten hydrogen bonds and face-to-face π-stacking interactions in the solid state, while 3·2b is stabilized by four hydrogen bonds and face-to-face π-stacking interactions. As well as in the X-ray structure of 1·2c, a water molecule acts as a hydrogen bridge between the β-pyridinium protons of 2a and the ether oxygen atoms of 1 in 1·2a. The successful preparation of 1·2a demonstrated that the tert-butyl group is not big enough to be a stopper for rotaxanes based on 1.
Keywordshost-guest system-self-assembly-pseudorotaxane-cryptand-paraquat
Science China-Chemistry 04/2012; 53(4):858-862. · 1.02 Impact Factor
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ABSTRACT: Investigation of extracts from the plant Athroisma proteiforme (Humbert) Mattf. (Asteraceae) for antimalarial activity led to the isolation of the five new sesquiterpene lactones 1-5 together with centaureidin (6). The structures of the new compounds were deduced from analyses of physical and spectroscopic data, and the absolute configuration of compound 1 was confirmed by an X-ray crystallographic study. Athrolides C (3) and D (4) both showed antiplasmodial activities with IC50 values of 6.6 (3) and 7.2 μM (4) against the HB3 strain and 5.5 (3) and 4.2 μM (4) against the Dd2 strain of the malarial parasite Plasmodium falciparum. The isolates 1-6 also showed antiproliferative activity against A2780 human ovarian cancer cells, with IC50 values ranging from 0.4 to 2.5 μM.
Journal of Natural Products 10/2011; 74(10):2174-80. · 3.13 Impact Factor
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ABSTRACT: A series of compounds designed to adopt a conformation similar to the tubulin-binding T-Taxol conformation of the anticancer drug paclitaxel has been synthesized. Both the internally bridged analogs 37-39, 41 and the open-chain analogs 27-29 and 43 were prepared. The bridged analogs 37-39 and 41 were synthesized by Grubbs' metatheses of compounds 30-32 and 33, which, in turn, were prepared by coupling β-lactams 24-26 with alcohols 22 and 23. Both the bridged and the open-chain analogs showed moderate to good cytotoxicity.
Bioorganic & medicinal chemistry 10/2011; 19(24):7664-78. · 2.82 Impact Factor
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ABSTRACT: Investigation of extracts from the plant Athroisma proteiforme (Humbert) Mattf. (Asteraceae) for antimalarial activity led to the isolation of the five new sesquiterpene lactones 1–5 together with centaureidin (6). The structures of the new compounds were deduced from analyses of physical and spectroscopic data, and the absolute configuration of compound 1 was confirmed by an X-ray crystallographic study. Athrolides C (3) and D (4) both showed antiplasmodial activities with IC50 values of 6.6 (3) and 7.2 μM (4) against the HB3 strain and 5.5 (3) and 4.2 μM (4) against the Dd2 strain of the malarial parasite Plasmodium falciparum. The isolates 1–6 also showed antiproliferative activity against A2780 human ovarian cancer cells, with IC50 values ranging from 0.4 to 2.5 μM.
10/2011;
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Organic Letters 09/2011; · 5.86 Impact Factor
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Organic Letters 09/2011; · 5.86 Impact Factor
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Organic Letters 09/2011; · 5.86 Impact Factor
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ABSTRACT: The first pseudocryptand-type supramolecular [3]pseudorotaxane was designed and prepared via the self-assembly of a bispicolinate BMP32C10 derivative and a bisparaquat. The complexation behavior was cooperative. In addition, the complex comprised of the BMP32C10 derivative and a cyclic bisparaquat demonstrated strong binding; interestingly, a poly[2]pseudocatenane structure was formed in the solid state for the first time.
Organic Letters 08/2011; 13(17):4616-9. · 5.86 Impact Factor
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ABSTRACT: The first dual component pseudocryptand-type [2]pseudorotaxanes were designed and prepared via the self-assembly of synthetically easily accessible bis(meta-phenylene)-32-crown-10 pyridyl, quinolyl, and naphthyridyl derivatives with paraquat. The formation of the pseudocryptand structures in the complexes remarkably improved the association constant by forming the third pseudobridge via H-bonding with the guest and π-stacking of the heterocyclic units.
Organic Letters 06/2011; 13(15):3992-5. · 5.86 Impact Factor
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ABSTRACT: By the self-assembly of a bis(meta-phenylene)-32-crown-10 bearing two electron-donating groups (carbazoles) with electron-accepting paraquat derivatives, the first [2]pseudorotaxane and the first pseudocryptand-type poly[2]pseudorotaxane based on bis(meta-phenylene)-32-crown-10 were isolated as crystalline solids as shown by X-ray analyses.
Organic Letters 06/2011; 13(11):2872-5. · 5.86 Impact Factor
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ABSTRACT: Complexation of anions, cations and even ion pairs is now an active area of investigation in supramolecular chemistry; unfortunately it is an area fraught with complications when these processes are examined in low polarity organic media. Using a pseudorotaxane complex as an example, apparent K(a2) values (=[complex]/{[salt](o) -[complex]}{[host](o) -[complex]}) for pseudorotaxane formation from dibenzylammonium salts (2-X) and dibenzo-[24]crown-8 (1, DB24C8) in CDCl(3) /CD(3) CN 3:2 vary with concentration. This is attributable to the fact that the salt is ion paired, but the complex is not. We report an equilibrium model that explicitly includes ion pair dissociation and is based upon activities rather than molar concentrations for study of such processes in non-aqueous media. Proper analysis requires both a dissociation constant, K(ipd) , for the salt and a binding constant for interaction of the free cation 2(+) with the host, K(a5) ; K(a5) for pseudorotaxane complexation is independent of the counterion (500 M(-1) ), a result of the complex existing in solution as a free cation, but K(ipd) values for the salts vary by nearly two orders of magnitude from trifluoroacetate to tosylate to tetrafluoroborate to hexafluorophosphate anions. The activity coefficients depend on the nature of the predominant ions present, whether the pseudorotaxane or the ions from the salt, and also strongly on the molar concentrations; activity coefficients as low as 0.2 are observed, emphasizing the magnitude of their effect. Based on this type of analysis, a method for precise determination of relative binding constants, K(a5) , for multiple hosts with a given guest is described. However, while the incorporation of activity coefficients is clearly necessary, it removes the ability to predict from the equilibrium constants the effects of concentration on the extent of binding, which can only be determined experimentally. This has serious implications for study of all such complexation processes in low polarity media.
Chemistry 02/2011; 17(11):3192-206. · 5.93 Impact Factor
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Liva Harinantenaina,
Peggy J Brodie, Carla Slebodnick,
Martin W Callmander,
Etienne Rakotobe,
Sennen Randrianasolo,
Richard Randrianaivo,
Vincent E Rasamison,
Karen Tendyke,
Yongchun Shen,
Edward M Suh,
David G I Kingston
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ABSTRACT: Bioassay-guided fractionation of an ethanol extract of the roots of the endemic Malagasy plant Pongamiopsis pervilleana led to the isolation of the three new compounds (2'R)-4'-hydroxyemoroidocarpan (1), pongavilleanine (3), and epipervilline (4) together with two known compounds, identified as emoroidocarpan (2) and rotenolone (5). The structures of all compounds were determined by physical, chemical, and spectroscopic evidence. The stereochemistry at C-2' of the previously reported compound emoroidocarpan was determined to be R by the observation of a negative Cotton effect at 474 nm in the CD spectrum of its osmate ester derivative. Compounds 2-5 displayed moderate antiproliferative activity against the A2780 human ovarian cancer cell line, and rotenolone also showed micromolar antiproliferative activity toward the breast cancer BT-549, prostate cancer DU 145, NSCLC NCI-H460, and colon cancer HCC-2998 cell lines.
Journal of Natural Products 09/2010; 73(9):1559-62. · 3.13 Impact Factor
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ABSTRACT: A series of N,N-alkylene bis(N'-alkylimidazolium) salts with various anions was prepared and characterized. The hydrogen-bonding abilities and ion-pairing strengths of the salts in solution were varied by changing the solvent and anion. Qualitatively, the extent of ion pairing of the 1,2-bis[N-(N'-butylimidazolium)]ethane salts with different anions was determined in acetone-d(6) by (1)H NMR spectroscopy. Thermal properties of the imidazolium salts were related not only to the nature of anions but also to the spacer length between imidazolium cations. Exceptionally high melting points of 1,2-bis[N-(N'-alkylimidazolium)]ethane bis(hexafluorophosphate)s can be explained by multiple hydrogen bonds observed in the X-ray crystal structures. Moreover, a trans conformation of the ethylene spacer of 1,2-bis[N-(N'-alkylimidazolium)]ethane bis(hexafluorophosphate)s allows good stacking structure in the crystals.
The Journal of Physical Chemistry B 06/2010; 114(21):7312-9. · 3.70 Impact Factor
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Journal of Polymer Science Part A Polymer Chemistry 01/2010; 48(4):975 - 985. · 3.92 Impact Factor
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ABSTRACT: Enantiopure amino-acid derived 1H-benzo[e][1,4]diazepin-2(3H)-ones (BZDs) undergo highly retentive deprotonation/alkylation reactions. To confirm the role of stereolabile, axially chiral intermediates in these reactions and to determine the precise stereochemical course of deprotonation and alkylation, a new alanine-derived BZD (S)-1d was prepared. Because of slow diazepine ring inversion of the C3-alkylated derivatives of 1d, it proved possible to determine that electrophiles react at the concave face of the enolate derived from 1d. Furthermore, an enantiopure silyl enol ether derivative of (S)-1d was prepared and characterized by X-ray crystallography, confirming that deprotonation resulted in an (M)-configured axially chiral enolate. Activation parameters for diazepine ring inversion in the potassium enolate of 1d were determined experimentally and are well-matched by density functional calculations. Finally, the factors leading to concave-face alkylation of the enolate derived from 1d are analyzed based on calculated alkylation transition structures. Minimization of torsional effects at the BZD ring fusion and maximization of imine and amide resonance are proposed to favor concave-face alkylation.
Journal of the American Chemical Society 11/2009; 131(50):18168-76. · 9.91 Impact Factor
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Chunying Shu,
Wei Xu, Carla Slebodnick,
Hunter Champion,
Wujun Fu,
Jonathan E Reid,
Hugo Azurmendi,
Chunru Wang,
Kim Harich,
Harry C Dorn,
Harry W Gibson
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ABSTRACT: Two new 6,6-open phenyl-C(81)-butyric acid methyl ester metallofulleroids, M(3)N@C(80)PCBM (M = Sc, Y), were synthesized by diazoalkane addition reactions and fully characterized. The results demonstrate that the reactive sites are the same for M(3)N@C(80) (M = Sc, Y) but dramatically different from that of C(60).
Organic Letters 05/2009; 11(8):1753-6. · 5.86 Impact Factor
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ABSTRACT: Each of the two novel title transition metal coordination polymers, namely catena-poly[[bis{[tris(2-pyridylmethyl)amine]cobalt(II)}-mu(4)-7,7,8,8-tetracyanoquinodimethanide(2-)] bis[7,7,8,8-tetracyanoquinodimethanide(1-)] methanol disolvate], {[Co(2)(C(12)H(4)N(4))(C(18)H(18)N(4))(2)](C(12)H(4)N(4))(2).2CH(3)OH}(n), (I), and catena-poly[[[[tris(2-pyridylmethyl)amine]iron(II)]-mu(2)-7,7,8,8-tetracyanoquinodimethanide(2-)] methanol solvate], {[Fe(C(12)H(4)N(4))(C(18)H(18)N(4))].CH(3)OH}(n), (II), contains eta(4)-TPA and cis-bridging TCNQ(2-) ligands [TPA is tris(2-pyridylmethyl)amine and TCNQ is 7,7,8,8-tetracyanoquinodimethane], but the two compounds adopt entirely different structural motifs. Compound (I) consists of a ribbon coordination polymer featuring mu(4)-TCNQ(2-) radical anion ligands bridging four different octahedral Co(II) centers. Each formula unit of the polymer is flanked by two uncoordinated TCNQ(-) anions and two methanol solvent molecules. All three TCNQ anions have crystallographic inversion symmetry. In (II), the 2(1) symmetry operator generates a one-dimensional zigzag chain of octahedral Fe(II) centers with mu(2)-TCNQ(2-) bridges. A methanol solvent molecule forms hydrogen bonds to one of the terminal N atoms of the bridging TCNQ(2-) dianion. To the best of our knowledge, these are the first examples of one-dimensional coordination polymers forming from cis coordination of two TCNQ ligands to octahedral metal centers.
Acta crystallographica. Section C, Crystal structure communications 02/2009; 65(Pt 1):m28-32. · 0.78 Impact Factor
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ABSTRACT: Six epothilone D analogues with a bridge between the C4-methyl and the C12-methyl carbons were prepared in an attempt to constrain epothilone D to its proposed tubulin-binding conformation. Ring-closing metathesis (RCM) was employed as the key step to build the C4-C26 bridge. In antiproliferative assays in the human ovarian cancer (A2780) and prostate cancer (PC3) cell lines, and also in tubulin assembly assay, all these compounds proved to be less active than epothilone D.
Organic & Biomolecular Chemistry 01/2009; 6(24):4542-52. · 3.70 Impact Factor
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Chunying Shu, Carla Slebodnick,
Liaosa Xu,
Hunter Champion,
Tim Fuhrer,
Ting Cai,
Jonathan E Reid,
Wujun Fu,
Kim Harich,
Harry C Dorn,
Harry W Gibson
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ABSTRACT: Photochemically generated benzyl radicals react with Sc(3)N@C(80)-I(h) to produce a dibenzyl adduct [Sc(3)N@C(80)(CH(2)C(6)H(5))(2)] in 82% yield and high regioselectivity. The adduct's (1)H spectrum revealed high symmetry: only one AB pattern was observed for the methylene protons. The (13)C NMR spectrum suggested a C(2)-symmetrical structure. DFT calculations reveal that a 1,4-adduct is more favorable than a 1,2-adduct by >10 kcal/mol. The 1,4-structure on [566] ring junctions was unambiguously confirmed by X-ray crystallographic analysis. UV-vis spectra revealed that the removal of two p orbitals from the pi system of the cage together with the benzylic substituents change the electronic properties of the metallofullerene in a manner similar to those reported for disilirane and trifluoromethyl moieties. Under the same conditions from Lu(3)N@C(80)-I(h) we prepared (63% yield) Lu(3)N@C(80)(CH(2)C(6)H(5))(2), which demonstrated properties similar to the 1,4-dibenzyl adduct of Sc(3)N@C(80)-I(h).
Journal of the American Chemical Society 01/2009; 130(52):17755-60. · 9.91 Impact Factor
