TY - JOUR A1 - Kleinpeter, Erich A1 - Heydenreich, Matthias A1 - Koch, Andreas A1 - Linker, Torsten T1 - Synthesis and NMR spectroscopic conformational analysis of esters of 4-hydroxy-cyclohexanone-the more polar the molecule the more stable the axial conformer N2 - 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. Y1 - 2012 SN - 0040-4020 ER - TY - JOUR A1 - Csütörtöki, Renáta A1 - Szatmári, István A1 - Koch, Andreas A1 - Heydenreich, Matthias A1 - Kleinpeter, Erich A1 - Fulop, Ferenc T1 - Synthesis and conformational analysis of new naphth[1,2-e][1,3]oxazino[3,4-c]quinazoline derivatives Y1 - 2011 SN - 0040-4020 ER - TY - JOUR A1 - Szatmari, Istvan A1 - Heydenreich, Matthias A1 - Koch, Andreas A1 - Fulop, Ferenc A1 - Kleinpeter, Erich T1 - Unexpected isomerization of new naphth[1,3]oxazino[2,3-a] isoquinolines in solution, studied by dynamic NMR and supported by theoretical DFT computations JF - Tetrahedron N2 - Through the reactions of 1-aminomethyl-2-naphthol and substituted 1-aminobenzyl-2-naphthols with 3,4-dihydroisoquinoline or 6,7-dimethoxy-3,4-dihydroisoquinoline under microwave conditions, naphth[1,2-e][1,3]oxazino[2,3-a]-isoquinoline derivatives were prepared in good yields. The latter reaction was extended by using 2-aminoarylmethyl-1-naphthols, leading to isomeric naphth-[2,1-e][1,3]oxazino[2,3-a] isoquinolines. Beside the detailed NMR spectroscopic and theoretical study of both stereochemistry and dynamic behaviour of these new conformational flexible heterocyclic ring systems an unexpected dynamic process between two diastereomers was observed in solution, studied by variable temperature H-1 NMR spectroscopy and the mechanism proved by theoretical DFT computations. KW - 3,4-Dihydroisoquinoline KW - Aminonaphthol KW - Dynamic NMR spectroscopy KW - DFT calculations KW - Conformational analysis Y1 - 2013 U6 - https://doi.org/10.1016/j.tet.2013.06.094 SN - 0040-4020 VL - 69 IS - 35 SP - 7455 EP - 7465 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Nitschke, Felix A1 - Wang, Peixiang A1 - Schmieder, Peter A1 - Girard, Jean-Marie A1 - Awrey, Donald E. A1 - Wang, Tony A1 - Israelian, Johan A1 - Zhao, XiaoChu A1 - Turnbull, Julie A1 - Heydenreich, Matthias A1 - Kleinpeter, Erich A1 - Steup, Martin A1 - Minassian, Berge A. T1 - Hyperphosphorylation of glucosyl C6 carbons and altered structure of glycogen in the neurodegenerative epilepsy lafora disease JF - Cell metabolism N2 - Laforin or malin deficiency causes Lafora disease, characterized by altered glycogen metabolism and teenage-onset neurodegeneration with intractable and invariably fatal epilepsy. Plant starches possess small amounts of metabolically essential monophosphate esters. Glycogen contains similar phosphate amounts, which are thought to originate from a glycogen synthase error side reaction and therefore lack any specific function. Glycogen is also believed to lack monophosphates at glucosyl carbon C6, an essential phosphorylation site in plant starch metabolism. We now show that glycogen phosphorylation is not due to a glycogen synthase side reaction, that C6 is a major glycogen phosphorylation site, and that C6 monophosphates predominate near centers of glycogen molecules and positively correlate with glycogen chain lengths. Laforin or malin deficiency causes C6 hyperphosphorylation, which results in malformed long-chained glycogen that accumulates in many tissues, causing neurodegeneration in brain. Our work advances the understanding of Lafora disease pathogenesis and suggests that glycogen phosphorylation has important metabolic function. Y1 - 2013 U6 - https://doi.org/10.1016/j.cmet.2013.04.006 SN - 1550-4131 SN - 1932-7420 VL - 17 IS - 5 SP - 756 EP - 767 PB - Cell Press CY - Cambridge ER - TY - JOUR A1 - Machumi, Francis A1 - Yenesew, Abiy A1 - Midiwo, Jacob O. A1 - Heydenreich, Matthias A1 - Kleinpeter, Erich A1 - Tekwani, Babu L. A1 - Khan, Shabana I. A1 - Walker, Larry A. A1 - Muhammad, Ilias T1 - Antiparasitic and anticancer carvotacetone derivatives of Sphaeranthus bullatus JF - Natural product communications : an international journal for communications and reviews N2 - 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. KW - Sphaeranthus bullatus KW - Asteraceae KW - Antiplasmodial KW - Antileishmanial KW - Anticancer KW - Carvotacetones Y1 - 2012 SN - 1934-578X VL - 7 IS - 9 SP - 1123 EP - 1126 PB - NPC CY - Westerville ER - TY - JOUR A1 - Csuetoertoeki, Renata A1 - Szatmari, Istvan A1 - Heydenreich, Matthias A1 - Koch, Andreas A1 - Starke, Ines A1 - Fueloep, Ferenc A1 - Kleinpeter, Erich T1 - Novel piperidine-fused benzoxazino- and quinazolinonaphthoxazines-synthesis and conformational study JF - TETRAHEDRON N2 - 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. KW - Quinazolines KW - Naphthoxazines KW - DFT structural study KW - Conformational analysis KW - NMR spectroscopy Y1 - 2012 U6 - https://doi.org/10.1016/j.tet.2012.05.048 SN - 0040-4020 VL - 68 IS - 31 SP - 6284 EP - 6288 PB - PERGAMON-ELSEVIER SCIENCE LTD CY - OXFORD ER - TY - JOUR A1 - Kleinpeter, Erich A1 - Heydenreich, Matthias A1 - Koch, Andreas A1 - Linker, Torsten T1 - Synthesis and NMR spectroscopic conformational analysis of esters of 4-hydroxy-cyclohexanone-the more polar the molecule the more stable the axial conformer JF - Tetrahedron N2 - 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. KW - 4-Substituted cyclohexanones KW - Conformational analysis KW - Dynamic NMR KW - Simulation of H-1 NMR spectra KW - Quantum chemical calculations KW - ALTONA equation Y1 - 2012 U6 - https://doi.org/10.1016/j.tet.2012.01.022 SN - 0040-4020 VL - 68 IS - 10 SP - 2363 EP - 2373 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Csuetoertoeki, Renata A1 - Szatmari, Istvan A1 - Koch, Andreas A1 - Heydenreich, Matthias A1 - Kleinpeter, Erich A1 - Fueloep, Ferenc T1 - Synthesis and conformational analysis of new naphth[1,2-e][1,3]oxazino[3,4-c]quinazoline derivatives JF - Tetrahedron N2 - A new highly functionalized aminonaphthol derivative, 1-(amino(2-aminophenyl)methyl)-2-naphthol (4), was synthesized by the reaction of 2-naphthol, 2-nitrobenzaldehyde and tert-butyl carbamate or benzyl carbamate, followed by reduction and/or removal of the protecting group. The aminonaphthol derivative thus obtained was converted in ring-closure reactions with formaldehyde. benzaldehyde and/or phosgene to the corresponding naphth[1,2-e][1,3]oxazino[3,4-c]quinazoline derivatives. The conformational analysis of some derivatives by NMR spectroscopy and accompanying molecular modelling are also reported. KW - Naphthoxazinoquinazolines KW - NMR KW - Conformational analysis KW - DFT calculations KW - Hammett-Brown plots Y1 - 2011 U6 - https://doi.org/10.1016/j.tet.2011.08.074 SN - 0040-4020 VL - 67 IS - 44 SP - 8564 EP - 8571 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Marsat, Jean-Noel A1 - Heydenreich, Matthias A1 - Kleinpeter, Erich A1 - Berlepsch, Hans V. A1 - Boettcher, Christoph A1 - Laschewsky, André T1 - Self-Assembly into multicompartment micelles and selective solubilization by Hydrophilic-Lipophilic-Fluorophilic block copolymers JF - Macromolecules : a publication of the American Chemical Society N2 - Amphiphilic linear ternary block copolymers (ABC) were synthesized in three consecutive steps by the reversible addition fragmentation chain transfer (RAFT) method. Using oligo(ethylene oxide) monomethyl ether acrylate, benzyl acrylate, and 1H,1H-perfluorobutyl acrylate monomers, the triblock copolymers consist of a hydrophilic (A), a lipophilic (B), and a fluorophilic (C) block. The block sequence of the triphilic copolymers was varied systematically to provide all possible variations: ABC, ACB, and BAC. All blocks have glass transition temperatures below 0 degrees C. Self-assembly into spherical micellar aggregates was observed in aqueous solution, where hydrophobic cores undergo local phase separation into various ultrastructures as shown by cryogenic transmission electron microscopy (cryo-TEM). Selective solubilization of substantial quantities of hydrocarbon and fluorocarbon low molar mass compounds by the lipophilic and fluorophilic block, respectively, is demonstrated. Y1 - 2011 U6 - https://doi.org/10.1021/ma200032j SN - 0024-9297 VL - 44 IS - 7 SP - 2092 EP - 2105 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Shainyan, Bagrat A. A1 - Moskalik, Mikhail Yu A1 - Heydenreich, Matthias A1 - Kleinpeter, Erich T1 - Conformational equilibrium and dynamic behavior of bis-N-triflyl substituted 3,8-diazabicyclo[3.2.1]octane JF - Magnetic resonance in chemistry N2 - Restricted rotation about the N-S partial double bonds in a bis-N-triflyl substituted 3,8-diazabicyclo[3.2.1]octane derivative 1 has been frozen at low temperature (Delta G* = 11.6 kcal mol(-1)), and the existence of all four rotamers about the two N-S bonds, 3-in, 8-in, 3-in, 8-out, 3-out, 8-in, and 3-out, 8-out, respectively, proved experimentally by NMR spectroscopy and theoretically by DFT and MP2 calculations. Copyright (C) 2014 John Wiley & Sons, Ltd. KW - NMR KW - H-1 KW - C-13 KW - F-19 KW - Dynamic NMR KW - Conformational equilibrium KW - restricted N-S rotation Y1 - 2014 U6 - https://doi.org/10.1002/mrc.4086 SN - 0749-1581 SN - 1097-458X VL - 52 IS - 8 SP - 448 EP - 452 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Buyinza, Daniel A1 - Derese, Solomon A1 - Ndakala, Albert A1 - Heydenreich, Matthias A1 - Yenesew, Abiy A1 - Koch, Andreas A1 - Oriko, Richard T1 - A coumestan and a coumaronochromone from Millettia lasiantha JF - Biochemical systematics and ecology N2 - The manuscript describes the phytochemical investigation of the roots, leaves and stem bark of Millettia lasiantha resulting in the isolation of twelve compounds including two new isomeric isoflavones lascoumestan and las-coumaronochromone. The structures of the new compounds were determined using different spectroscopic techniques. KW - Millettia lasiantha KW - Leguminosae KW - Coumestan KW - Coumaronochromone Y1 - 2021 U6 - https://doi.org/10.1016/j.bse.2021.104277 SN - 0305-1978 SN - 1873-2925 VL - 97 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Barta, Petra A1 - Szatmari, Istvan A1 - Fueloep, Ferenc A1 - Heydenreich, Matthias A1 - Koch, Andreas A1 - Kleinpeter, Erich T1 - Synthesis and stereochemistry of new naphth[1,3]oxazino[3,2-a] benzazepine and naphth[1,3]oxazino[3,2-e]thienopyridine derivatives JF - Tetrahedron N2 - Through the reactions of 1- or 2-naphthol and 4,5-dihydro-3H-benz[c]azepine or 6,7-dihydrothieno[3,2-c]pyridine, new aminonaphthol derivatives were prepared. The syntheses were extended by using N-containing naphthol analogues such as 5-hydroxyisoquinoline and 6-hydroxyquinoline. The ring closures of the novel bifunctional compounds were also achieved, resulting in new naphth[2,1-e][1,3]oxazines, naphth[1,2-e][1,3]oxazines, isoquinolino[5,6-e][1,3]oxazines and quinolino[5,6-e][1,3]oxazines. H-1 NMR spectra of the target heterocycles 16, 20 and 21 were sufficiently resolved to indentify the present stereochemistry; therefore, beside computed structures, spatial experimental (dipolar coupling-NOE) and computed (ring current effect of the naphthyl moiety-TSNMRS) NMR studies were employed. The studied heterocycles exist exclusively as S(14b),R(N), R(14b),S(N), and S(16b)S(N) isomers, respectively. The flexible moieties of the studied compounds prefer. (C) 2016 Elsevier Ltd. All rights reserved. KW - Modified Mannich reaction KW - Thienopyridine KW - Benzazepine KW - NMR spectroscopy KW - Stereochemistry KW - Theoretical calculations Y1 - 2016 U6 - https://doi.org/10.1016/j.tet.2016.03.058 SN - 0040-4020 VL - 72 SP - 2402 EP - 2410 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Kleinpeter, Erich A1 - Heydenreich, Matthias A1 - Koch, Andreas A1 - Krtitschka, Angela A1 - Krüger, Tobias A1 - Linker, Torsten T1 - NMR spectroscopic conformational analysis of 4-methylene-cyclohexyl pivalateThe effect of sp(2) hybridization JF - Magnetic resonance in chemistry N2 - The conformational equilibrium of the axial/equatorial conformers of 4-methylene-cyclohexyl pivalate is studied by dynamic NMR spectroscopy in a methylene chloride/freon mixture. At 153K, the ring interconversion gets slow on the nuclear magnetic resonance timescale, the conformational equilibrium (-G degrees) can be examined, and the barrier to ring interconversion (G(#)) can be determined. The structural influence of sp(2) hybridization on both G degrees and G(#) of the cyclohexyl moiety can be quantified. KW - 4-methylene-cyclohexyl pivalate KW - conformational analysis KW - dynamic NMR spectroscopy KW - exo-methylene conformational effect at cyclohexane KW - quantum chemical calculations Y1 - 2017 U6 - https://doi.org/10.1002/mrc.4630 SN - 0749-1581 SN - 1097-458X VL - 55 SP - 1073 EP - 1078 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Szatmari, Istvan A1 - Belasri, Khadija A1 - Heydenreich, Matthias A1 - Koch, Andreas A1 - Kleinpeter, Erich A1 - Fulop, Ferenc T1 - Ortho-Quinone methide driven synthesis of new O,N- or N,N-Heterocycles JF - ChemistryOpen : including thesis treasury N2 - To synthesize functionalized Mannich bases that can serve two different types of ortho-quinone methide (o-QM) intermediates, 2-naphthol and 6-hydroxyquinoline were reacted with salicylic aldehyde in the presence of morpholine. The Mannich bases that can form o-QM and aza-o-QM were also synthesized by mixing 2-naphthol, 2-nitrobenzaldehyde, and morpholine followed by reduction of the nitro group. The highly functionalized aminonaphthol derivatives were then tested in [4+2] cycloaddition with different cyclic imines. The reaction proved to be both regio- and diastereoselective. In all cases, only one reaction product was obtained. Detailed structural analyses of the new polyheterocycles as well as conformational studies including DFT modelling were performed. The relative stability of o-QMs/aza-o-QM were also calculated, and the regioselectivity of the reactions could be explained only when the cycloaddition started from aminodiol 4. It was summarized that starting from diaminonaphthol 25, the regioselectivity of the reaction is driven by the higher nucleophilicity of the amino group compared with the hydroxy group. 12H-benzo[a]xanthen-12-one (11), formed via o-QM formation, was isolated as a side product. The proton NMR spectrum of 11 proved to be very unique from NMR point of view. The reason for the extreme low-field position of proton H-1 could be accounted for by theoretical calculation of structure and spatial magnetic properties of the compound in combination of ring current effects of the aromatic moieties and steric compression within the heavily hindered H(1)-C(1)-C(12b)-C(12a)-C(12)=O structural fragment. KW - ortho-quinone methide (o-QMs) KW - modified Mannich reaction KW - cycloaddition KW - NMR spectroscopy KW - conformational analysis KW - DFT calculations Y1 - 2019 U6 - https://doi.org/10.1002/open.201900150 SN - 2191-1363 VL - 8 IS - 7 SP - 961 EP - 971 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Shainyan, Bagrat A. A1 - Suslova, Elena N. A1 - Tran Dinh Phien, A1 - Shlykov, Sergey A. A1 - Heydenreich, Matthias A1 - Kleinpeter, Erich T1 - 1-Methylthio-1-phenyl-1-silacyclohexane: Synthesis, conformational preferences in gas and solution by GED, NMR and theoretical calculations JF - Tetrahedron N2 - 1-Methylthio-1-phenyl-1-silacyclohexane 1, the first silacyclohexane with the sulfur atom at silicon, was synthesized and its molecular structure and conformational preferences studied by gas-phase electron diffraction (GED) and low temperature C-13 and Si-29 NMR spectroscopy (LT NMR). Quantum-chemical calculations were carried out both for the isolated species and solvate complexes in gas and in polar medium. The predominance of the 1-MeSaxPheq conformer in gas phase (1-Ph-eq :1-Ph-ax = 55:45, Delta G degrees = 0.13 kcal/mol) determined from GED is consistent with that measured in the freon solution by LT NMR (1-Ph-eq:1-Ph-ax = 65:35, Delta G degrees = 0.12 kcal/mol), the experimentally measured ratios being close to that estimated by quantum chemical calculations at both the DFT and MP2 levels of theory. (C) 2019 Elsevier Ltd. All rights reserved. KW - 1-Methylthio-1-phenyl-1-silacyclohexane KW - Conformational analysis KW - Gas phase electron diffraction KW - Low-temperature C-13 and Si-29 NMR KW - DFT and MP2 calculations Y1 - 2019 U6 - https://doi.org/10.1016/j.tet.2019.130677 SN - 0040-4020 VL - 75 IS - 46 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Kleinpeter, Erich A1 - Heydenreich, Matthias A1 - Shainyan, Bagrat A. T1 - At the experimental limit of the NMR conformational analysis BT - Si-29 and C-13 NMR study of the conformational equilibrium of 1-phenyl-1-tert-butylsilacyclohexane JF - Organic letters N2 - The low temperature (95 K) NMR study of 1-Ph-1-t-Bu-silacyclohexane (1) showed the conformational equilibrium to be extremely one-sided toward thePh(ax),t-Bueq conformer. The barrier to interconversion has been measured (4.2-4.6 kcal/mol) and the conformational equilibrium [Delta nu = 1990.64 ppm (Si-29), 618.9 ppm (C-13), 1-Ph-ax:1-Pheq = (95.6-96.6%):(3.4-4.4%), K = 25 +/- 3, Delta G degrees = -RT ln K = 0.58-0.63 kcal/mol] analyzed. The assignment and quantification of the NMR signals is supported by MP2 and DFT calculations. Y1 - 2021 U6 - https://doi.org/10.1021/acs.orglett.0c03878 SN - 1523-7060 SN - 1523-7052 VL - 23 IS - 2 SP - 405 EP - 409 PB - American Chemical Society CY - Washington ER -