@article{MachumiYenesewMidiwoetal.2012, author = {Machumi, Francis and Yenesew, Abiy and Midiwo, Jacob O. and Heydenreich, Matthias and Kleinpeter, Erich and Tekwani, Babu L. and Khan, Shabana I. and Walker, Larry A. and Muhammad, Ilias}, title = {Antiparasitic and anticancer carvotacetone derivatives of Sphaeranthus bullatus}, series = {Natural product communications : an international journal for communications and reviews}, volume = {7}, journal = {Natural product communications : an international journal for communications and reviews}, number = {9}, publisher = {NPC}, address = {Westerville}, issn = {1934-578X}, pages = {1123 -- 1126}, year = {2012}, abstract = {The CH2Cl2-MeOH (1:1) extract of the aerial parts of Sphaeranthus bullatus, an annual herb native to tropical East Africa, showed activity against chloroquine sensitive D6 (IC50 9.7 mu g/mL) and chloroquine resistant W2 (IC50 15.0 mu g/mL) strains of Plasmodium falciparum. Seventeen secondary metabolites were isolated from the extract through conventional chromatographic techniques and identified using various spectroscopic methods. The compounds were evaluated for their in vitro antiplasmodial, antileishmanial and anticancer activities revealing activity of four carvotacetone derivatives, namely 3-acetoxy-7-hydroxy-5-tigloyloxycarvotacetone (1) 3,7-dihydroxy-5-tigloyloxycarvotacetone (2), 3-acetoxy-5,7-dihydroxycarvotacetone (3) and 3,5,7-trihydroxycarvotacetone (4); with antiplasmodial IC50 values of 1.40, 0.79, 0.60 and 3.40 mu g/mL, respectively, against chloroquine sensitive D6 strains of P. falciparum; antiplasmodial activity of IC50 2.00, 0.90, 0.68 and 2.80 mu g/mL respectively, against chloroquine resistant W2 strains of P. falciparum, antileishmanial IC50, values of 0.70, 3.00, 0.70 and 17.00 mu g/mL, respectively, against the parasite L. donovanii promastigotes, and anticancer activity against human SK-MEL, KB, BT-549 and SK-OV-3 tumor cells, with IC50 values between <1.1 - 5.3 mu g/mL, for 1-3. In addition, cytotoxic effects of the active compounds were evaluated against monkey kidney fibroblasts (VERO) and pig kidney epithelial cells (LLC-PK11). The structures of carvotacetone derivatives were determined by ID and 2D NMR spectroscopy; the absolute stereochemical configuration of 3-acetoxy-7-hydroxy-5-tigloyloxycarvotacetone (I) was determined as 3R, 4R, 5S by circular dichroism, specific rotation, H-1 NMR and 2D NMR ROESY and NOESY experiments.}, language = {en} } @article{KleinpeterHeydenreichKochetal.2012, author = {Kleinpeter, Erich and Heydenreich, Matthias and Koch, Andreas and Linker, Torsten}, title = {Synthesis and NMR spectroscopic conformational analysis of esters of 4-hydroxy-cyclohexanone-the more polar the molecule the more stable the axial conformer}, issn = {0040-4020}, year = {2012}, abstract = {The esters of 4-hydroxy-cyclohexanone and a series of carboxylic acids R-COOH with R of different electronic and steric influence (R=Me, Et, n-Pr, i-Pr, n-Bu, i-Bu, sec-Bu, t-Bu, CF3, CH2Cl, CHCl2, CCl3, CH2Br, CHBr2, and CBr3) were synthesized and the conformational equilibria studied by 1H and 13C NMR spectroscopy at 103 K and at 295 K, respectively. The geometry of optimized structures of the axial/equatorial chair conformers was computed at the ab initio MO and DFT levels of theory. Only one preferred conformation was obtained for the axial and the equatorial conformer as well. When comparing the conformational equilibria of the cyclohexanone esters with those of the corresponding cyclohexyl esters a certain polarity contribution of the cyclohexanone framework was revealed, which is independent of the substituent effects and increases the stability of the axial conformers by a constant amount.}, language = {en} } @article{KleinpeterHeydenreichKochetal.2012, author = {Kleinpeter, Erich and Heydenreich, Matthias and Koch, Andreas and Linker, Torsten}, title = {Synthesis and NMR spectroscopic conformational analysis of esters of 4-hydroxy-cyclohexanone-the more polar the molecule the more stable the axial conformer}, series = {Tetrahedron}, volume = {68}, journal = {Tetrahedron}, number = {10}, publisher = {Elsevier}, address = {Oxford}, issn = {0040-4020}, doi = {10.1016/j.tet.2012.01.022}, pages = {2363 -- 2373}, year = {2012}, abstract = {The esters of 4-hydroxy-cyclohexanone and a series of carboxylic acids R-COOH with R of different electronic and steric influence (R=Me, Et, n-Pr, i-Pr, n-Bu, i-Bu, sec-Bu, t-Bu, CF3, CH2Cl, CHCl2, CCl3, CH2Br, CHBr2, and CBr3) were synthesized and the conformational equilibria studied by H-1 and C-13 NMR spectroscopy at 103 K and at 295 K, respectively. The geometry of optimized structures of the axial 'equatorial chair conformers was computed at the ab initio MO and DFT levels of theory. Only one preferred conformation was obtained for the axial and the equatorial conformer as well. When comparing the conformational equilibria of the cyclohexanone esters with those of the corresponding cyclohexyl esters a certain polarity contribution of the cyclohexanone framework was revealed, which is independent of the substituent effects and increases the stability of the axial conformers by a constant amount.}, language = {en} } @article{KleinpeterCsuetoertoekiSzatmarietal.2012, author = {Kleinpeter, Erich and Cs{\"u}t{\"o}rt{\"o}ki, Ren{\´a}ta and Szatm{\´a}ri, Istv{\´a}n and Heydenreich, Matthias and Koch, Andreas and Starke, Ines and Fulop, Ferenc}, title = {Novel piperidine-fused benzoxazino- and quinazolinonaphthoxazines-synthesis and conformational study}, issn = {0040-4020}, year = {2012}, abstract = {The reactions of 1-(amino(2-hydroxyphenyl)methyl)-2-naphthol (3) and 1-(amino(2-aminophenyl)methyl)-2-naphthol (6) with glutardialdehyde resulted in the formation of piperidine-fused benzoxazinonaphthoxazine 4 and quinazolinonaphthoxazine 7, respectively, both in diastereopure form. The full conformational search protocols of 4 and 7 were successfully carried out by NMR spectroscopy and accompanying molecular modelling; the global minimum-energy conformers of all diastereomers were computed, and the assignments of the most stable stereoisomers, Gtct1 for 4 and Gtct1 for 7, were corroborated by spatial NOE information relating to the H7a-H10a-H15b and H,H coupling patterns of the protons in the flexible part of the piperidine moiety. Additionally, mass spectrometric fragmentation was investigated in collision-induced dissociation experiments. The elemental compositions of the ions were determined by accurate mass measurements.}, language = {en} } @article{CsuetoertoekiSzatmariKochetal.2012, author = {Cs{\"u}t{\"o}rt{\"o}ki, Renata and Szatmari, Istvan and Koch, Andreas and Heydenreich, Matthias and Kleinpeter, Erich and Fulop, Ferenc}, title = {Syntheses and conformational analyses of new naphth[1,2-e][1,3]oxazino[3,2-c] quinazolin-13-ones}, series = {Tetrahedron}, volume = {68}, journal = {Tetrahedron}, number = {24}, publisher = {Elsevier}, address = {Oxford}, issn = {0040-4020}, doi = {10.1016/j.tet.2012.04.026}, pages = {4600 -- 4608}, year = {2012}, abstract = {The syntheses of naphth[1,2-e][1,3]oxazino[3,2-c]quinazolin-13-one derivatives (3a-f) were achieved by the solvent-free heating of benzyloxycarbonyl-protected intermediates (2a-f) with MeONa. For intermediates 2a-f, prepared by the reactions of substituted aminonaphthols with benzyl N-(2-formylphenyl)carbamate, not only the expected trans ring form B and chain form A(1), but also the rearranged chain form A(2) as a new tautomer were detected in DMSO at room temperature. The quantity of A(2) in the tautomeric mixture was changed with time. Conformational analyses of the target heterocycles 3a-f by NMR spectroscopy and accompanying theoretical calculations at the DFT level of theory revealed that the oxazine ring preferred a twisted chair conformation and the quinazolone ring was planar. Besides the conformations, both the configurations at C-7a and C-15 and the preferred rotamers of the 1-naphthyl substituent at C-15 were assigned, which allowed evaluation of the aryl substituent-dependent steric hindrance in this part of the molecules. Configurational assignments were corroborated by quantifying the ring current effect of 15-aryl in terms of spatial NICS.}, language = {en} } @article{CsuetoertoekiSzatmariHeydenreichetal.2012, author = {Csuetoertoeki, Renata and Szatmari, Istvan and Heydenreich, Matthias and Koch, Andreas and Starke, Ines and Fueloep, Ferenc and Kleinpeter, Erich}, title = {Novel piperidine-fused benzoxazino- and quinazolinonaphthoxazines-synthesis and conformational study}, series = {TETRAHEDRON}, volume = {68}, journal = {TETRAHEDRON}, number = {31}, publisher = {PERGAMON-ELSEVIER SCIENCE LTD}, address = {OXFORD}, issn = {0040-4020}, doi = {10.1016/j.tet.2012.05.048}, pages = {6284 -- 6288}, year = {2012}, abstract = {The reactions of 1-(amino(2-hydroxyphenyl)methyl)-2-naphthol (3) and 1-(amino(2-aminophenyl) methyl)-2-naphthol (6) with glutardialdehyde resulted in the formation of piperidine-fused benzox-azinonaphthoxazine 4 and quinazolinonaphthoxazine 7, respectively, both in diastereopure form. The full conformational search protocols of 4 and 7 were successfully carried out by NMR spectroscopy and accompanying molecular modelling; the global minimum-energy conformers of all diastereomers were computed, and the assignments of the most stable stereoisomers, G(tct)(1) for 4 and G(tct)(1) for 7, were corroborated by spatial NOE information relating to the H-7a-H-10a-H-15b and H,H coupling patterns of the protons in the flexible part of the piperidine moiety. Additionally, mass spectrometric fragmentation was investigated in collision-induced dissociation experiments. The elemental compositions of the ions were determined by accurate mass measurements. (C) 2012 Elsevier Ltd. All rights reserved.}, language = {en} } @inproceedings{MachumiYenesewMidiwoetal.2012, author = {Machumi, F. and Yenesew, Abiy and Midiwo, J. O. and Heydenreich, Matthias and Kleinpeter, Erich and Khan, S. and Tekwani, B. L. and Walker, L. A. and Muhammad, I}, title = {Antiparasitic and anticancer carvotacetone derivatives from Sphaeranthus bullatus}, series = {Planta medica : journal of medicinal plant and natural product research}, volume = {78}, booktitle = {Planta medica : journal of medicinal plant and natural product research}, number = {11}, publisher = {Thieme}, address = {Stuttgart}, issn = {0032-0943}, pages = {1201 -- 1202}, year = {2012}, language = {en} }