TY - JOUR A1 - Fudickar, Werner A1 - Bauch, Marcel A1 - Ihmels, Heiko A1 - Linker, Torsten T1 - DNA-triggered enhancement of singlet oxygen production by pyridinium alkynylanthracenes JF - Chemistry - a European journal N2 - There is an ongoing interest in O-1(2) sensitizers, whose activity is selectively controlled by their interaction with DNA. To this end, we synthesized three isomeric pyridinium alkynylanthracenes 2 o-p and a water-soluble trapping reagent for O-1(2). In water and in the absence of DNA, these dyes show a poor efficiency to sensitize the photooxygenation of the trapping reagent as they decompose due to electron transfer processes. In contrast, in the presence of DNA O-1(2) is generated from the excited DNA-bound ligand. The interactions of 2 o-p with DNA were investigated by thermal DNA melting studies, UV/vis and fluorescence spectroscopy, and linear and circular dichroism spectroscopy. Our studies revealed an intercalative binding with an orientation of the long pyridyl-alkynyl axis parallel to the main axis of the DNA base pairs. In the presence of poly(dA : dT), all three isomers show an enhanced formation of singlet oxygen, as indicated by the reaction of the latter with the trapping reagent. With green light irradiation of isomer 2 o in poly(dA : dT), the conversion rate of the trapping reagent is enhanced by a factor >10. The formation of O-1(2) was confirmed by control experiments under anaerobic conditions, in deuterated solvents, or by addition of O-1(2) quenchers. When bound to poly(dG : dC), the opposite effect was observed only for isomers 2 o and 2 m, namely the trapping reagent reacted significantly slower. Overall, we showed that pyridinium alkynylanthracenes are very useful intercalators, that exhibit an enhanced photochemical O-1(2) generation in the DNA-bound state. KW - Anthracene KW - DNA KW - intercalations KW - photochemistry KW - singlet oxygen Y1 - 2021 U6 - https://doi.org/10.1002/chem.202101918 SN - 1521-3765 VL - 27 IS - 54 SP - 13591 EP - 13604 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Krüger, Tobias A1 - Linker, Torsten T1 - Synthesis of gamma-spirolactams by Birch reduction of arenes JF - European journal of organic chemistry N2 - A convenient method for the synthesis of gamma-spirolactams in only three steps is described. Birch reduction of inexpensive and commercially available aromatic carboxylic acids in the presence of chloroacetonitrile affords nitriles in moderate to good yields. Suitable precursors are methyl-substituted benzoic acids, naphthoic, and anthroic acid. Subsequent catalytic hydrogenation proceeds smoothly with PtO2 or Raney Ni as catalysts and lactams are isolated in excellent yields and stereoselectivities. Thus, up to 3 new stereogenic centers can be constructed as sole diastereomers from achiral benzoic acids. Furthermore, it is possible to control the degree of saturation at different pressures, affording products with 0, 1, or 2 double bonds. Overall, more than 15 new gamma-spirolactams have been synthesized in analytically pure form. KW - Arenes KW - Birch reduction KW - Hydrogenation KW - Lactams KW - Synthetic methods Y1 - 2021 U6 - https://doi.org/10.1002/ejoc.202100056 SN - 1099-0690 VL - 2021 IS - 10 SP - 1585 EP - 1591 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Fudickar, Werner A1 - Linker, Torsten T1 - Structural motives controlling the binding affinity of 9,10-bis(methylpyridinium)anthracenes towards DNA JF - Bioorganic & medicinal chemistry : a Tetrahedron publication for the rapid dissemination of full original research papers and critical reviews on biomolecular chemistry, medicinal chemistry and related disciplines N2 - In the search of new DNA groove binding agents a series of substituted 9,10-methylpyridiniumanthracenes have been synthesized and their interactions with DNA have been studied by UV/vis absorption, CD and fluorescence spectroscopy. A minor groove binding mode is confirmed by DNA melting studies, strong CD effects, the dependence of the binding affinity on ionic strength, and the differentiation between AT and GC base pairs. No binding occurs to GC sequences. Binding constants to calf thymus DNA (ct-DNA) and poly(dA:dT) in the range between 1 x 10(4) and 3 x 10(5) M-1 have been determined. The binding strength decreases with the size of substituents attached at the anthracene site. Variation of the substitution pattern of the charged groups shows that methyl groups in meta position cause slightly stronger binding than methyl groups in para position. In contrast, with these groups in ortho position, no binding interaction has been observed. The strongest binding is achieved with an expansion of the peripheral heterocycle from pyridine to quinoline. Molecular modeling reveals the pivotal role of the substitution pattern: Anthracenes with para and meta pyridines align along the minor grooves. On the other hand, the ortho derivative adopts no groove-alignment. KW - groove binding KW - anthracenes KW - ct-DNA KW - fluorescence enhancement KW - docking Y1 - 2020 U6 - https://doi.org/10.1016/j.bmc.2020.115432 SN - 0968-0896 SN - 1464-3391 VL - 28 IS - 8 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Fudickar, Werner A1 - Metz, Melanie A1 - Mai-Linde, Yasemin A1 - Krüger, Tobias A1 - Kelling, Alexandra A1 - Sperlich, Eric A1 - Linker, Torsten T1 - Influence of functional groups on the ene reaction of singlet oxygen with 1,4-cyclohexadienes JF - Photochemistry and photobiology : the official journal of the American Society for Photobiology N2 - The photooxygenation of 1,4-cyclohexadienes has been studied with a special focus on regio- and stereoselectivities. In all examples, only the methyl-substituted double bond undergoes an ene reaction with singlet oxygen, to afford hydroperoxides in moderate to good yields. We explain the high regioselectivities by a "large-group effect" of the adjacent quaternary stereocenter. Nitriles decrease the reactivity of singlet oxygen, presumably by quenching, but can stabilize proposed per-epoxide intermediates by polar interactions resulting in different stereoselectivities. Spiro lactams and lactones show an interesting effect on regio- and stereoselectivities of the ene reactions. Thus, singlet oxygen attacks the double bond preferentially anti to the carbonyl group, affording only one regioisomeric hydroperoxide. If the reaction occurs from the opposite face, the other regioisomer is exclusively formed by severe electrostatic repulsion in a perepoxide intermediate. We explain this unusual behavior by the fixed geometry of spiro compounds and call it a "spiro effect" in singlet oxygen ene reactions. Y1 - 2021 U6 - https://doi.org/10.1111/php.13422 SN - 0031-8655 SN - 1751-1097 VL - 97 IS - 6 SP - 1289 EP - 1297 PB - Wiley CY - Malden, Mass. ER - TY - JOUR A1 - Haubitz, Toni A1 - Fudickar, Werner A1 - Linker, Torsten A1 - Kumke, Michael Uwe T1 - pH-sensitive fluorescence switching of pyridylanthracenes BT - the effect of the isomeric pattern JF - The journal of physical chemistry : A, Molecules, spectroscopy, kinetics, environment & general theory N2 - 9,10-substituted anthracenes are known for their useful optical properties like fluorescence, which makes them frequently used probes in sensing applications. In this article, we investigate the fundamental photophysical properties of three pyridyl-substituted variants. The nitrogen atoms in the pyridinium six-membered rings are located in the ortho-, meta-, and para-positions in relation to the anthracene core. Absorption, fluorescence, and transient absorption measurements were carried out and were complemented by theoretical calculations. We monitored the photophysics of the anthracene derivatives in chloroform and water investigating the protonated as well as their nonprotonated forms. We found that the optical properties of the nonprotonated forms are strongly determined by the anthracene chromophore, with only small differences to other 9,10-substituted anthracenes, for example diphenyl anthracene. In contrast, protonation leads to a strong decrease in fluorescence intensity and lifetime. Transient absorption measurements and theoretical calculations revealed the formation of a charge-transfer state in the protonated chromophores, where electron density is shifted from the anthracene moiety toward the protonated pyridyl substituents. While the para- and ortho-derivatives' charge transfer is still moderately fluorescent, the meta-derivative is affected much stronger and shows nearly no fluorescence. This nitrogen-atom-position-dependent sensitivity to hydronium activity makes a combination of these fluorophores very attractive for pH-sensing applications covering a broadened pH range. KW - Absorption KW - Aromatic compounds KW - Fluorescence KW - Hydrocarbons KW - Reaction mechanisms Y1 - 2020 U6 - https://doi.org/10.1021/acs.jpca.0c09911 SN - 1089-5639 SN - 1520-5215 VL - 124 IS - 52 SP - 11017 EP - 11024 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Mai-Linde, Yasemin A1 - Linker, Torsten T1 - Radical clock probes to determine carbohydrate radical stabilities JF - Organic letters N2 - Carbohydrate radical stabilities in the 1- and 2-position have been determined by a radical clock approach, starting from cyclopropanated sugars with xanthates as precursors. Various hexoses and pentoses afforded 1-deoxy sugars as main products, indicating that anomeric radicals are more stable than radicals in the 2-position. An additional influence of the configurations on radical stabilities has been observed. Our results should be interesting for the understanding of 1,2-radical rearrangements in carbohydrate chemistry and offer an easy access to deoxy-vinyl sugars. KW - stereoselective-synthesis KW - convenient synthesis KW - chemistry KW - cyclopropanation KW - mechanism KW - glycals KW - beta-(acyloxy)alkylrear KW - rangement KW - sugars Y1 - 2020 U6 - https://doi.org/10.1021/acs.orglett.0c00111 SN - 1523-7060 SN - 1523-7052 VL - 22 IS - 4 SP - 1525 EP - 1529 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Fudickar, Werner A1 - Roder, Phillip A1 - Listek, Martin A1 - Hanack, Katja A1 - Linker, Torsten T1 - Pyridinium alkynylanthracenes as sensitizers for photodynamic therapy JF - Photochemistry and photobiology N2 - Photodynamic therapy (PDT) is a mild but effective method to treat certain types of cancer upon irradiation with visible light. Here, three isomeric methylpyridinium alkynylanthracenes 1op were evaluated as sensitizers for PDT. Upon irradiation with blue or green light, all three compounds show the ability to initiate strand breaks of plasmid DNA. The mayor species responsible for cleavage is singlet oxygen (O-1(2)) as confirmed by scavenging reagents. Only isomers 1m and 1p can be incorporated into HeLa cells, whereas isomer 1o cannot permeate through the membrane. While isomer 1m targets the cell nucleus, isomer 1p assembles in the cellular cytoplasm and impacts the cellular integrity. This is in accordance with a moderate toxicity of 1p in the dark, whereas 1m exhibits no dark toxicity. Both isomers are suitable as PDT reagents, with a CC50 of 3 mu m and 75 nm, for 1p and 1m, respectively. Thus, derivative 1m, which can be easily synthesized, becomes an interesting candidate for cancer therapy. Y1 - 2021 U6 - https://doi.org/10.1111/php.13554 SN - 0031-8655 SN - 1751-1097 VL - 98 IS - 1 SP - 193 EP - 201 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Fudickar, Werner A1 - Linker, Torsten T1 - Photooxygenation of naphthalene JF - ChemPhotoChem N2 - The photooxygenation of naphthalene to the corresponding endoperoxide (EPO) under various conditions is described. Substantial conversion is only observed at -10 degrees C and after more than two days, indicating that the [4+2] cycloaddition of singlet oxygen to this acene proceeds much more slowly than corresponding reactions of substituted naphthalenes, a rate constant of k = 5.4 +/- 0.3 M(-1)s(-1) was determined by competition kinetics. Another problem is the thermal lability and photochemical cleavage of the naphthalene EPO. We investigated the mechanism of this radical process depending on the light source and sensitizer in comparison to known cyclohexadiene EPO. Thus, bisepoxides and keto epoxides are formed after homolysis of the O-O bond by irradiation with sodium lamps or blue LEDs and subsequent cyclization. This process is accelerated by the sensitizers methylene blue and 9,10-dicyanoanthracene, indicating an electron transfer mechanism. Finally, the cleavage of the peroxidic bond is inhibited with red LEDs, and photooxygenation under such conditions affords 20 % EPO. Thus, we could demonstrate that contrary to literature statements singlet oxygen does indeed react with naphthalene. KW - naphthalene KW - photooxygenation KW - reaction mechanisms KW - reactive KW - intermediates KW - singlet oxygen Y1 - 2021 U6 - https://doi.org/10.1002/cptc.202100097 VL - 5 IS - 11 SP - 1004 EP - 1008 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Krüger, Tobias A1 - Bramborg, Andrea A1 - Kelling, Alexandra A1 - Sperlich, Eric A1 - Linker, Torsten T1 - Birch Reduction of Arenes as an Easy Entry to γ-Spirolactones JF - European journal of organic chemistry N2 - A convenient method for the synthesis of γ-spirolactones in only 2–3 steps is described. Birch reduction of inexpensive and commercially available aromatic carboxylic acids in the presence of ethylene oxide affords hydroxy acids, which undergo direct lactonization during work-up. Suitable precursors are methyl-substituted benzoic acids, naphthoic, and dicarboxylic acids. Subsequent hydrogenation proceeds smoothly with Pd/C as catalyst and saturated γ-spirolactones are isolated in excellent yields and stereoselectivities. Thus, up to 3 new stereogenic centers can be constructed as sole diastereomers from achiral benzoic acids. Furthermore, it is possible to control the degree of saturation with Raney nickel or Wilkinson's catalyst to obtain products with 1 double bond. Overall, more than 30 new γ-spirolactones have been synthesized in analytically pure form. KW - Arenes KW - Birch reduction KW - Hydrogenation KW - Lactones KW - Synthetic methods Y1 - 2021 U6 - https://doi.org/10.1002/ejoc.202101018 SN - 1434-193X SN - 1099-0690 VL - 2021 IS - 46 SP - 6383 EP - 6391 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Krüger, Tobias A1 - Kelling, Alexandra A1 - Schilde, Uwe A1 - Linker, Torsten T1 - Simple Synthesis of gamma-Spirolactams by Birch Reduction of Benzoic Acids JF - European journal of organic chemistry N2 - A convenient synthesis of gamma-spirolactams in only two steps was developed. Birch reduction of benzoic acids and immediate alkylation with chloroacetonitrile afforded cyclohexadienes in high yields. The products could be isolated by crystallization on a large scale in analytically pure form. Subsequent hydrogenation with platinum(IV) oxide as the catalyst reduced the nitrile functionality and the double bonds in the same step with excellent stereoselectivity. The relative configurations were determined unequivocally by X-ray analyses. Direct cyclization of the intermediary formed amino acids afforded the desired gamma-spirolactams in excellent overall yields. The procedure is characterized by few steps, cheap reagents, and can be performed on a large scale, interesting for industrial processes. KW - Diastereoselectivity KW - Hydrogenation KW - Lactams KW - Reduction KW - Synthetic methods Y1 - 2016 U6 - https://doi.org/10.1002/ejoc.201601650 SN - 1434-193X SN - 1099-0690 IS - 6 SP - 1074 EP - 1077 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Tian, Guang-Zong A1 - Hu, Jing A1 - Zhang, Heng-Xi A1 - Rademacher, Christoph A1 - Zou, Xiao-Peng A1 - Zheng, Hong-Ning A1 - Xu, Fei A1 - Wang, Xiao-Li A1 - Linker, Torsten A1 - Yin, Jian T1 - Synthesis and conformational analysis of linear homo- and heterooligomers from novel 2-C-branched sugar amino acids (SAAs) JF - Scientific reports N2 - Sugar amino acids (SAAs), as biologically interesting structures bearing both amino and carboxylic acid functional groups represent an important class of multifunctional building blocks. In this study, we develop an easy access to novel SAAs in only three steps starting from nitro compounds in high yields in analytically pure form, easily available by ceric (IV) mediated radical additions. Such novel SAAs have been applied in the assembly of total nine carbopeptoids with the form of linear homo-and heterooligomers for the structural investigations employing circular dichroism (CD) spectroscopy, which suggest that the carbopeptoids emerge a well-extended, left (or right)-handed conformation similar to polyproline II (PPII) helices. NMR studies also clearly demonstrated the presence of ordered secondary structural elements. 2D-ROESY spectra were acquired to identify i+1NH <-> (C1H)-C-i, (C2H)-C-i correlations which support the conformational analysis of tetramers by CD spectroscopy. These findings provide interesting information of SAAs and their oligomers as potential scaffolds for discovering new drugs and materials. Y1 - 2018 U6 - https://doi.org/10.1038/s41598-018-24927-6 SN - 2045-2322 VL - 8 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Geroldinger, Gerald A1 - Tonner, Matthias A1 - Fudickar, Werner A1 - De Sarkar, Sritama A1 - Dighal, Aishwarya A1 - Monzote, Lianet A1 - Staniek, Katrin A1 - Linker, Torsten A1 - Chatterjee, Mitali A1 - Gille, Lars T1 - Activation of anthracene endoperoxides in leishmania and impairment of mitochondrial functions JF - Molecules N2 - Leishmaniasis is a vector-borne disease caused by protozoal Leishmania. Because of resistance development against current drugs, new antileishmanial compounds are urgently needed. Endoperoxides (EPs) are successfully used in malaria therapy, and experimental evidence of their potential against leishmaniasis exists. Anthracene endoperoxides (AcEPs) have so far been only technically used and not explored for their leishmanicidal potential. This study verified the in vitro efficiency and mechanism of AcEPs against both Leishmania promastigotes and axenic amastigotes (L. tarentolae and L. donovani) as well as their toxicity in J774 macrophages. Additionally, the kinetics and radical products of AcEPs’ reaction with iron, the formation of radicals by AcEPs in Leishmania, as well as the resulting impairment of parasite mitochondrial functions were studied. Using electron paramagnetic resonance combined with spin trapping, photometry, and fluorescence-based oximetry, AcEPs were demonstrated to (i) show antileishmanial activity in vitro at IC50 values in a low micromolar range, (ii) exhibit host cell toxicity in J774 macrophages, (iii) react rapidly with iron (II) resulting in the formation of oxygen- and carbon-centered radicals, (iv) produce carbon-centered radicals which could secondarily trigger superoxide radical formation in Leishmania, and (v) impair mitochondrial functions in Leishmania during parasite killing. Overall, the data of different AcEPs demonstrate that their structures besides the peroxo bridge strongly influence their activity and mechanism of their antileishmanial action. KW - Leishmania KW - endoperoxides KW - EPR spectroscopy KW - mitochondria KW - radicals Y1 - 2018 U6 - https://doi.org/10.3390/molecules23071680 SN - 1420-3049 VL - 23 IS - 7 PB - MDPI CY - Basel ER - TY - JOUR A1 - Fudickar, Werner A1 - Linker, Torsten T1 - Release of Singlet Oxygen from Organic Peroxides under Mild Conditions JF - ChemPhotoChem N2 - Singlet oxygen can be released in the dark in nearly quantitative yield from endoperoxides of naphthalenes, anthracenes and pyridones as an alternative to its generation by photosensitization. Recently, new donor systems have been designed which operate at very low temperatures but which are prepared from their parent forms at acceptable rates. Enhancement of the reactivity of donors is conveniently achieved by the design of the substitution pattern or through the use of plasmonic heating of nanoparticle-bound donors. The most important aim of these donor molecules is to transfer singlet oxygen in a controlled and directed manner to a target. Low temperatures and the linking between donors and acceptors reduce the random walk of oxygen and may force an attack at the desired position. By using chiral donor systems, new stereocenters might be introduced into prochiral acceptors. KW - donor-acceptor systems KW - oxygenation KW - peroxides KW - polycycles KW - retro reactions Y1 - 2018 U6 - https://doi.org/10.1002/cptc.201700235 SN - 2367-0932 VL - 2 IS - 7 SP - 548 EP - 558 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Fudickar, Werner A1 - Linker, Torsten T1 - Release of Singlet Oxygen from Aromatic Endoperoxides by Chemical Triggers JF - Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition N2 - The generation of reactive singlet oxygen under mild conditions is of current interest in chemistry, biology, and medicine. We were able to release oxygen from dipyridylanthracene endoperoxides (EPOs) by using a simple chemical trigger at low temperature. Protonation and methylation of such EPOs strongly accelerated these reactions. Furthermore, the methyl pyridinium derivatives are water soluble and therefore serve as oxygen carriers in aqueous media. Methylation of the EPO of the ortho isomer affords the parent form directly without increasing the temperature under very mild conditions. This exceptional behavior is ascribed to the close contact between the nitrogen atom and the peroxo group. Singlet oxygen is released upon this reaction, and can be used to oxygenate an acceptor such as tetramethylethylene in the dark with no heating. Thus, a new chemical source of singlet oxygen has been found, which is triggered by a simple stimulus. KW - anthracenes KW - donor-acceptor systems KW - mild reaction conditions KW - selective oxidations KW - singlet oxygen Y1 - 2018 U6 - https://doi.org/10.1002/anie.201806881 SN - 1433-7851 SN - 1521-3773 VL - 57 IS - 39 SP - 12971 EP - 12975 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Bauch, Marcel A1 - Fudickar, Werner A1 - Linker, Torsten T1 - Stereoselective [4+2] Cycloaddition of Singlet Oxygen to Naphthalenes Controlled by Carbohydrates JF - Molecules : a journal of synthetic chemistry and natural product chemistry N2 - Stereoselective reactions of singlet oxygen are of current interest. Since enantioselective photooxygenations have not been realized efficiently, auxiliary control is an attractive alternative. However, the obtained peroxides are often too labile for isolation or further transformations into enantiomerically pure products. Herein, we describe the oxidation of naphthalenes by singlet oxygen, where the face selectivity is controlled by carbohydrates for the first time. The synthesis of the precursors is easily achieved starting from naphthoquinone and a protected glucose derivative in only two steps. Photooxygenations proceed smoothly at low temperature, and we detected the corresponding endoperoxides as sole products by NMR. They are labile and can thermally react back to the parent naphthalenes and singlet oxygen. However, we could isolate and characterize two enantiomerically pure peroxides, which are sufficiently stable at room temperature. An interesting influence of substituents on the stereoselectivities of the photooxygenations has been found, ranging from 51:49 to up to 91:9 dr (diastereomeric ratio). We explain this by a hindered rotation of the carbohydrate substituents, substantiated by a combination of NOESY measurements and theoretical calculations. Finally, we could transfer the chiral information from a pure endoperoxide to an epoxide, which was isolated after cleavage of the sugar chiral auxiliary in enantiomerically pure form. KW - singlet oxygen KW - photooxygenation KW - naphthalenes KW - carbohydrates KW - stereoselectivity KW - auxiliary control KW - [4+2] cycloaddition Y1 - 2021 U6 - https://doi.org/10.3390/molecules26040804 SN - 1420-3049 VL - 16 IS - 4 PB - MDPI CY - Basel ER - TY - GEN A1 - Bauch, Marcel A1 - Fudickar, Werner A1 - Linker, Torsten T1 - Stereoselective [4+2] Cycloaddition of Singlet Oxygen to Naphthalenes Controlled by Carbohydrates T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Stereoselective reactions of singlet oxygen are of current interest. Since enantioselective photooxygenations have not been realized efficiently, auxiliary control is an attractive alternative. However, the obtained peroxides are often too labile for isolation or further transformations into enantiomerically pure products. Herein, we describe the oxidation of naphthalenes by singlet oxygen, where the face selectivity is controlled by carbohydrates for the first time. The synthesis of the precursors is easily achieved starting from naphthoquinone and a protected glucose derivative in only two steps. Photooxygenations proceed smoothly at low temperature, and we detected the corresponding endoperoxides as sole products by NMR. They are labile and can thermally react back to the parent naphthalenes and singlet oxygen. However, we could isolate and characterize two enantiomerically pure peroxides, which are sufficiently stable at room temperature. An interesting influence of substituents on the stereoselectivities of the photooxygenations has been found, ranging from 51:49 to up to 91:9 dr (diastereomeric ratio). We explain this by a hindered rotation of the carbohydrate substituents, substantiated by a combination of NOESY measurements and theoretical calculations. Finally, we could transfer the chiral information from a pure endoperoxide to an epoxide, which was isolated after cleavage of the sugar chiral auxiliary in enantiomerically pure form. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1116 KW - singlet oxygen KW - photooxygenation KW - naphthalenes KW - carbohydrates KW - stereoselectivity KW - auxiliary control KW - [4+2] cycloaddition Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-493361 SN - 1866-8372 IS - 1116 ER - TY - JOUR A1 - Fudickar, Werner A1 - Linker, Torsten T1 - Theoretical insights into the effect of solvents on the [4+2] cycloaddition of singlet oxygen to substituted anthracenes BT - A change from a stepwise process to a concerted process JF - Journal of physical organic chemistry N2 - The [4 + 2] cycloadditions of singlet oxygen to 9,10-diphenylanthracene (1) and the meta and para isomers of 9,10-dipyridylanthracene (2m/p) and 9,10-methoxyphenylanthracene (3m/p) have been studied by density functional calculations in the gas phase at the UB3LYP/6-31G* level and for the first time in solvents at the conductor-like polarizable continuum model (CPCM) UM062X/6-31G* level. The differences in calculated transition state (TS) energies derived from this method are in line with experimentally observed reactivity orders in solution. For the gas-phase reaction, the first TS of the stepwise pathway (TS1) has biradical character, and its energy lies below the energy of the TS of the concerted path (TSconc). In contrast, in the solvent acetonitrile, TS1 resembles a zwitterion and lies significantly higher than the TSconc. Thus, a concerted mechanism applies in solvents, and the energy gap between the TS of the two processes decreases with decreasing polarity. A change from a pyridyl against a methoxyphenyl substituent in the para position causes a maximal reduction of the activation barrier by approximately 1.7 kcal/mol, resulting in a fivefold increased reactivity. KW - anthracenes KW - DFT calculations KW - endoperoxides KW - photooxygenation KW - singlet oxygen KW - solvent effect Y1 - 2019 U6 - https://doi.org/10.1002/poc.3951 SN - 0894-3230 SN - 1099-1395 VL - 32 IS - 7 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Fudickar, Werner A1 - Vomdran, Katja A1 - Linker, Torsten T1 - Auxiliary controlled singlet-oxygen ene reactions of cyclohexenes JF - Tetrahedron N2 - The photooxygenation of homochiral cyclohexene ketals, which are easily available from 2-cyclohexenone and L-tartrates, affords hydroperoxides and after reduction the corresponding allylic alcohols in good yields and high regioselectivities. This can be rationalized by electronic repulsions in a perepoxide intermediate and provides evidence for unfavorable 1,3 diaxial interactions with a dioxolane oxygen atom. Only low stereoselectivities were observed, due to the flexibility of the cyclohexene ring. However, the diastereomers could be separated and after cleavage of the auxiliary, 4-hydroxy-2-cyclohexen-1-one was isolated in enantiomerically pure form, which can serve as a building block for natural product synthesis. KW - singlet oxygen KW - auxiliary control KW - regioselectivity KW - stereoselectivity Y1 - 2006 U6 - https://doi.org/10.1016/j.tet.2006.07.104 SN - 0040-4020 VL - 62 IS - 46 SP - 10639 EP - 10646 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Bauch, Marcel A1 - Klaper, Matthias A1 - Linker, Torsten T1 - Intermediates in the cleavage of endoperoxides JF - Journal of physical organic chemistry N2 - The decomposition of anthracene endoperoxides has been investigated under various conditions. Thermolyses proceed via radical intermediates and afford anthracenes and rearrangement products, depending on the substitution pattern. Interestingly, not only the O-O but also the C-O bond can be cleaved homolytically. Under basic conditions fragmentations take place, affording anthraquinone, and reactive oxygen species. This mechanism explains the often observed decomposition of endoperoxides during work-up. Finally, an acid-catalyzed cleavage has been observed under release of hydrogen peroxide. The results should be interesting for the mechanistic understanding of peroxide decomposition and the endoperoxides might serve as mild sources of reactive oxygen species for future applications. Copyright (C) 2016 John Wiley & Sons, Ltd. KW - peroxides KW - radicals KW - reaction mechanism KW - reactive intermediates Y1 - 2017 U6 - https://doi.org/10.1002/poc.3607 SN - 0894-3230 SN - 1099-1395 VL - 30 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Fudickar, Werner A1 - Pavashe, Prashant A1 - Linker, Torsten T1 - Thiocarbohydrates on Gold Nanoparticles: Strong Influence of Stereocenters on Binding Affinity and Interparticle Forces JF - Chemistry - a European journal N2 - Carbohydrates carrying thiol groups at the C-2 position have been attached to gold nanoparticles (AuNPs) with stereocenters in close proximity to the surface for the first time. Their configurations can be clearly distinguished by the tendency of particle aggregation. AuNP surface plasmon resonance (SPR), X-ray photoelectron spectroscopy (XPS), and IR spectroscopy indicate that the thiocarbohydrates replace citrate molecules at different rates, causing aggregation and eventually precipitation. A quantitative formulation of this aggregation process shows that reactivities can vary by several magnitudes. Adsorption isotherms and kinetics also demonstrate that the number of thiocarbohydrates varies by a factor of two. Molecular mechanics force field (MMFF) calculations reveal their relative orientations. Based on these models, the different binding behavior can be ascribed to attractive van der Waals forces and hydrogen bonds. Such interactions occur either between the carbohydrate and AuNPs, by lateral intermolecular forces at the surface, or by interparticle attraction, in analogy to cell-surface carbohydrates of biological recognition systems. Aggregation of NPs therefore act as an indicator to differentiate between various carbohydrates with defined configurations. KW - carbohydrate recognition KW - citrate displacement KW - gold nanoparticles KW - plasmon spectroscopy KW - thiols Y1 - 2017 U6 - https://doi.org/10.1002/chem.201700846 SN - 0947-6539 SN - 1521-3765 VL - 23 SP - 8685 EP - 8693 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Kleinpeter, Erich A1 - Werner, Peter A1 - Linker, Torsten T1 - Synthesis and NMR spectroscopic conformational analysis of benzoic acid esters of mono- and 1,4-dihydroxycyclohexane, 4-hydroxycyclohexanone and the -ene analogue - The more polar the molecule the more stable the axial conformer JF - Tetrahedron N2 - para-Substituted benzoic acid esters of cyclohexanol, 1,4-dihydroxycyclohexane, 4-hydroxy-cyclohexanone and of the corresponding exo-methylene derivative were synthesized and the conformational equilibria of the cyclohexane skeleton studied by low temperature H-1 and C-13 NMR spectroscopy. The geometry optimized structures of the axial/equatorial chair conformers were computed at the DFT level of theory. Only one preferred conformation of the ester group was obtained for both the axial and the equatorial conformer, respectively. The content of the axial conformer increases with growing polarity of the 6-membered ring moiety; hereby, in addition, the effect of sp(2) hybridization/polarity of C(4)= O/C(4)= CH2 on the present conformational equilibria is critically evaluated. Another dynamic process could be studied, for the first time in this kind of compounds. (C) 2017 Elsevier Ltd. All rights reserved. KW - Conformational analysis KW - A-values of COOAr on cyclohexane KW - Benzoic acid esters KW - Dynamic NMR KW - DFT calculations Y1 - 2017 U6 - https://doi.org/10.1016/j.tet.2017.04.029 SN - 0040-4020 VL - 73 SP - 3801 EP - 3809 PB - Elsevier CY - Oxford ER - TY - GEN A1 - Ihmels, Heiko A1 - Linker, Torsten A1 - Trofimov, Aleksei T1 - Editorial T2 - Journal of physical organic chemistry Y1 - 2017 U6 - https://doi.org/10.1002/poc.3745 SN - 0894-3230 SN - 1099-1395 VL - 30 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Bauch, Marcel A1 - Krtitschka, Angela A1 - Linker, Torsten T1 - Photooxygenation of oxygen-substituted naphthalenes JF - Journal of physical organic chemistry N2 - The reaction of oxygen-substituted naphthalenes with singlet oxygen (O-1(2)) has been investigated, and labile endoperoxides have been isolated and characterized at -78 degrees C for the first time. Low-temperature kinetics by UV spectroscopy revealed that alkoxy and silyloxy substituents remarkably increase the rate of photooxygenations compared to 1,4-dimethylnaphthalene, whereas acyloxy-substituted acenes are inert towards O-1(2). The reactivities nicely correlate with HOMO energies and free activation energies, which we determined by density functional theory calculations. The lability of the isolated endoperoxides is due to their very fast back reaction to the corresponding naphthalenes even at -20 degrees C under release of O-1(2), making them to superior sources of this reactive species under very mild conditions. Finally, a carbohydrate-substituted naphthalene has been synthesized, which reacts reversibly with O-1(2) and might be applied for enantioselective oxidations in future work. KW - kinetics KW - labile peroxides KW - low-temperature experiments KW - naphthalenes KW - singlet oxygen Y1 - 2017 U6 - https://doi.org/10.1002/poc.3734 SN - 0894-3230 SN - 1099-1395 VL - 30 SP - 6803 EP - 6813 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Fudickar, Werner A1 - Linker, Torsten T1 - Synthesis of Pyridylanthracenes and Their Reversible Reaction with Singlet Oxygen to Endoperoxides JF - The journal of organic chemistry N2 - The ortho, meta, and para isomers of 9,10-dipyridylanthracene 1 have been synthesized and converted into their endoperoxides 1-O-2 upon oxidation with singlet oxygen. The kinetics of this reaction can be controlled by the substitution pattern and the solvent: in highly polar solvents, the meta isomer is the most reactive, whereas the ortho isomer is oxidized fastest in nonpolar solvents. Heating of the endoperoxides affords the parent anthracenes by release of singlet oxygen. Y1 - 2017 U6 - https://doi.org/10.1021/acs.joc.7b01765 SN - 0022-3263 VL - 82 SP - 9258 EP - 9262 PB - American Chemical Society CY - Washington 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 - Fudickar, Werner A1 - Linker, Torsten T1 - Imaging by sensitized oxygenations of photochromic anthracene films BT - Examination of effects that improve performance and reversibility JF - Chemistry - a European journal N2 - The aliphatic anthracene compound 1 and the oligomeric anthracene 2 were synthesized. Thin films of 1 and 2 mixed with the sensitizers tetraphenylporphyrin (TPP) and methylene blue (MB) were irradiated with visible light in air. Upon formation of singlet oxygen, the anthracene units were converted quantitatively to the corresponding endoperoxides. Heating of the irradiated samples afforded the parent anthracenes with high yields. Here, we demonstrate that the kinetics and reversibility of this reaction strongly depend on the microenvironment of the anthracene groups in the two compounds. The photooxidation of thin films of I is accompanied by interesting changes in the morphology of the film and allows the first application of 1 as a nondestructive negative-tone photo-resist for lithography and as an oxidizing ink. The morphology of 2 remained unchanged after photooxidation as a result of the stabilizing oligomer backbone. This stabilizing effect significantly improves the photochromic performance of 2. The reversibility of the photooxidation is very high (> 90%) for oligomeric films of 2 after several cycles of irradiation and beating. Decomposition of the anthracene and a loss of the activity of the sensitizer diminish slightly the performance of the monomeric species. KW - anthracenes KW - lithography KW - photochromism KW - singlet oxygen KW - thin films Y1 - 2006 U6 - https://doi.org/10.1002/chem.200600387 SN - 0947-6539 VL - 12 SP - 9276 EP - 9283 PB - WILEY‐VCH CY - Weinheim ER - TY - JOUR A1 - Linker, Torsten T1 - Addition of Heteroatom Radicals to endo-Glycals JF - Chemistry N2 - Radical reactions have found many applications in carbohydrate chemistry, especially in the construction of carbon–carbon bonds. The formation of carbon–heteroatom bonds has been less intensively studied. This mini-review will summarize the efforts to add heteroatom radicals to unsaturated carbohydrates like endo-glycals. Starting from early examples, developed more than 50 years ago, the importance of such reactions for carbohydrate chemistry and recent applications will be discussed. After a short introduction, the mini-review is divided in sub-chapters according to the heteroatoms halogen, nitrogen, phosphorus, and sulfur. The mechanisms of radical generation by chemical or photochemical processes and the subsequent reactions of the radicals at the 1-position will be discussed. This mini-review cannot cover all aspects of heteroatom-centered radicals in carbohydrate chemistry, but should provide an overview of the various strategies and future perspectives KW - radicals KW - carbohydrates KW - heteroatoms KW - synthesis Y1 - 2020 U6 - https://doi.org/10.3390/chemistry2010008 SN - 2624-8549 VL - 2 IS - 1 SP - 80 EP - 92 PB - MDPI CY - Basel ER - TY - GEN A1 - Linker, Torsten T1 - Addition of Heteroatom Radicals to endo-Glycals T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Radical reactions have found many applications in carbohydrate chemistry, especially in the construction of carbon–carbon bonds. The formation of carbon–heteroatom bonds has been less intensively studied. This mini-review will summarize the efforts to add heteroatom radicals to unsaturated carbohydrates like endo-glycals. Starting from early examples, developed more than 50 years ago, the importance of such reactions for carbohydrate chemistry and recent applications will be discussed. After a short introduction, the mini-review is divided in sub-chapters according to the heteroatoms halogen, nitrogen, phosphorus, and sulfur. The mechanisms of radical generation by chemical or photochemical processes and the subsequent reactions of the radicals at the 1-position will be discussed. This mini-review cannot cover all aspects of heteroatom-centered radicals in carbohydrate chemistry, but should provide an overview of the various strategies and future perspectives T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 873 KW - radicals KW - carbohydrates KW - heteroatoms KW - synthesis Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-459970 SN - 1866-8372 IS - 873 ER - TY - JOUR A1 - Klaper, Matthias A1 - Wessig, Pablo A1 - Linker, Torsten T1 - Base catalysed decomposition of anthracene endoperoxide JF - Chemical communications N2 - Catalytic amounts of a weak base are sufficient to induce the decomposition of anthracene endoperoxides to anthraquinone. The mechanism has been elucidated by isolation of intermediates in combination with DFT calculations. The whole process is suitable for the convenient generation of hydrogen peroxide under very mild conditions. Y1 - 2016 U6 - https://doi.org/10.1039/c5cc08606j SN - 1359-7345 SN - 1364-548X VL - 52 SP - 1210 EP - 1213 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Bauch, Marcel A1 - Böttcher, Dominique A1 - Bornscheuer, Uwe T. A1 - Linker, Torsten T1 - Enzymatic Cleavage of Aryl Acetates JF - ChemCatChem : heterogeneous & homogeneous & bio- & nano-catalysis ; a journal of ChemPubSoc Europe N2 - Seven enzymes have been screened for the cleavage of aryl acetates. Phenyl and naphthyl acetates react with lipases and esterases, whereas the sterically demanding anthracene acetate gave a conversion only with porcine liver esterase and esterase 2 from Bacillus subtilis (BS2). These two enzymes have been employed on a preparative (0.5 mmol) scale and afforded cleavage products in 91 and 94% yields, even for anthracene acetate. Thus, this method is superior to chemical cleavage with catalytic amounts of sodium methoxide (Zemplen conditions), which gave only low conversions. Finally, regioselectivity has been achieved with an anthracene bisacetate, in which an ethyl group controls the cleavage of the first acetate. This indicates that steric interactions play a crucial role in the enzymatic cleavage of aryl acetates, which might be interesting for future applications or the development of enzyme inhibitors. KW - arenes KW - enzyme catalysis KW - regioselectivity KW - steric hindrance KW - substituent effects Y1 - 2016 U6 - https://doi.org/10.1002/cctc.201600678 SN - 1867-3880 SN - 1867-3899 VL - 8 SP - 2853 EP - 2857 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Pavashe, Prashant A1 - Elamparuthi, Elangovan A1 - Hettrich, Cornelia A1 - Moeller, Heiko M. A1 - Linker, Torsten T1 - Synthesis of 2-Thiocarbohydrates and Their Binding to Concanavalin A JF - The journal of organic chemistry N2 - A convenient and general synthesis of 2-thiocarbohydrates via cerium ammonium nitrate oxidation of the thiocyanate ion is described. Radical addition to glycals proceeds with excellent regio- and good stereoselectivities in only one step, deprotection affords water-soluble 2-thio saccharides. Binding studies to Con A have been performed by isothermal titration calorimetry (ITC) and saturation transfer difference (STD) NMR spectroscopy. The 2-thiomannose derivative binds even stronger to Con A than the natural substrate, offering opportunities for new lectin or enzyme inhibitors. Y1 - 2016 U6 - https://doi.org/10.1021/acs.joc.6b00987 SN - 0022-3263 VL - 81 SP - 8595 EP - 8603 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Schilde, Uwe A1 - Kelling, Alexandra A1 - Umbreen, Sumaira A1 - Linker, Torsten T1 - Crystal structures of three bicyclic carbohydrate derivatives JF - Acta crystallographica, Section E, Crystallographic communications N2 - The title compounds, [(1R,3R,4R,5R,6S)-4,5-bis(acetyloxy)-7-oxo-2-oxabicyclo-[4.2.0]octan-3-yl]methyl acetate, C14H18O8, (I), [(1S,4R,5S,6R)-5-acetyloxy-7-hydroxyimino-2-oxobicyclo[4.2.0] octan-4-yl acetate, C11H15NO6, (II), and [(3aR, 5R, 6R, 7R, 7aS)-6,7-bis(acetyloxy)-2-oxooctahydropyrano[3,2-b]pyrrol-5-yl] methyl acetate, C14H19NO8, (III), are stable bicyclic carbohydrate derivatives. They can easily be synthesized in a few steps from commercially available glycals. As a result of the ring strain from the four-membered rings in (I) and (II), the conformations of the carbohydrates deviate strongly from the ideal chair form. Compound (II) occurs in the boat form. In the five-membered lactam (III), on the other hand, the carbohydrate adopts an almost ideal chair conformation. As a result of the distortion of the sugar rings, the configurations of the three bicyclic carbohydrate derivatives could not be determined from their NMR coupling constants. From our three crystal structure determinations, we were able to establish for the first time the absolute configurations of all new stereocenters of the carbohydrate rings. KW - crystal structure KW - carbohydrate derivatives KW - conformation KW - configuration Y1 - 2016 U6 - https://doi.org/10.1107/S2056989016018727 SN - 2056-9890 VL - 72 SP - 1839 EP - + PB - International Union of Crystallography CY - Chester ER - TY - JOUR A1 - Grott, Saskia A1 - Peter, Martin G. A1 - Linker, Torsten A1 - Sefkow, Michael A1 - Kroll, Jürgen A1 - Koetz, Joachim A1 - Laschewsky, André A1 - Lokatis, Siegfried A1 - Rheinberg, Falko A1 - Manig, Yvette T1 - Portal = Chemie: Werkstoffe, Wirkstoffe, Lebensvorgänge BT - Die Potsdamer Universitätszeitung N2 - Aus dem Inhalt: - Chemie: Werkstoffe, Wirkstoffe, Lebensvorgänge - Institut für Kirchenrecht gegründet - Computerlinguisten erstellen digitales Wörterbuch - Vom Spaß am Graffiti-Sprayen T3 - Portal: Das Potsdamer Universitätsmagazin - 01-02/2003 Y1 - 2003 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-439713 SN - 1618-6893 IS - 01-02/2003 ER - TY - JOUR A1 - Krueger, Tobias A1 - Kelling, Alexandra A1 - Linker, Torsten A1 - Schilde, Uwe T1 - Crystal structures of three cyclohexane‑based γ‑spirolactams BT - determination of configurations and conformations JF - BMC Chemistry N2 - The title compounds, 2-azaspiro[4.5]deca-1-one, C₉H₁₅NO, (1a), cis-8-methyl-2-azaspiro[4.5]deca-1-one, C₁₀H₁₇NO, (1b), and trans-8-methyl-2-azaspiro[4.5]deca-1-one, C₁₀H₁₇NO, (1c), were synthesized from benzoic acids 2 in only 3 steps in high yields. Crystallization from n-hexane afforded single crystals, suitable for X-ray diffraction. Thus, the configurations, conformations, and interesting crystal packing effects have been determined unequivocally. The bicyclic skeleton consists of a lactam ring, attached by a spiro junction to a cyclohexane ring. The lactam ring adopts an envelope conformation and the cyclohexane ring has a chair conformation. The main difference between compound 1b and compound 1c is the position of the carbonyl group on the 2-pyrrolidine ring with respect to the methyl group on the 8-position of the cyclohexane ring, which is cis (1b) or trans (1c). A remarkable feature of all three compounds is the existence of a mirror plane within the molecule. Given that all compounds crystallize in centrosymmetric space groups, the packing always contains interesting enantiomer-like pairs. Finally, the structures are stabilized by intermolecular N–H···O hydrogen bonds. KW - 2-Azaspiro[4.5]deca-1-ones KW - Cis- and trans-form KW - Configuration KW - Conformation KW - Lactams Y1 - 2019 U6 - https://doi.org/10.1186/s13065-019-0586-7 SN - 2661-801X VL - 13 IS - 69 PB - Springer International Publishing CY - Basel ER - TY - GEN A1 - Krueger, Tobias A1 - Kelling, Alexandra A1 - Linker, Torsten A1 - Schilde, Uwe T1 - Crystal structures of three cyclohexane‑based γ‑spirolactams BT - determination of configurations and conformations T2 - Postprints der Universität Potsdam Mathematisch-Naturwissenschaftliche Reihe N2 - The title compounds, 2-azaspiro[4.5]deca-1-one, C₉H₁₅NO, (1a), cis-8-methyl-2-azaspiro[4.5]deca-1-one, C₁₀H₁₇NO, (1b), and trans-8-methyl-2-azaspiro[4.5]deca-1-one, C₁₀H₁₇NO, (1c), were synthesized from benzoic acids 2 in only 3 steps in high yields. Crystallization from n-hexane afforded single crystals, suitable for X-ray diffraction. Thus, the configurations, conformations, and interesting crystal packing effects have been determined unequivocally. The bicyclic skeleton consists of a lactam ring, attached by a spiro junction to a cyclohexane ring. The lactam ring adopts an envelope conformation and the cyclohexane ring has a chair conformation. The main difference between compound 1b and compound 1c is the position of the carbonyl group on the 2-pyrrolidine ring with respect to the methyl group on the 8-position of the cyclohexane ring, which is cis (1b) or trans (1c). A remarkable feature of all three compounds is the existence of a mirror plane within the molecule. Given that all compounds crystallize in centrosymmetric space groups, the packing always contains interesting enantiomer-like pairs. Finally, the structures are stabilized by intermolecular N–H···O hydrogen bonds. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 738 KW - 2-Azaspiro[4.5]deca-1-ones KW - Cis- and trans-form KW - Configuration KW - Conformation KW - Lactams Y1 - 1019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-434911 IS - 738 ER - TY - JOUR A1 - Umbreen, Sumaira A1 - Linker, Torsten T1 - Simple Synthesis of Conformationally Fixed Glycosamine Analogues by Beckmann Rearrangement at the Carbohydrate Ring JF - Chemistry - a European journal N2 - Conformationally fixed carbohydrate analogues are promising small-molecule inhibitors for hydrolases like O-GlcNAcase (OGA); however, their synthesis usually requires many steps. Herein we describe cycloadditions of dichloroketene to various glycals and subsequent Beckmann rearrangements, which offer an easy and stereoselective entry to glycosamine derivatives in good yields. The reactions are applicable for hexoses, pentoses, and disaccharides, and transformations to the corresponding imidates proceed smoothly. First biological tests reveal that such imidates indeed inhibit human OGA. KW - carbohydrates KW - cycloaddition KW - enzyme inhibitors KW - rearrangement KW - selective syntheses Y1 - 2015 U6 - https://doi.org/10.1002/chem.201406546 SN - 0947-6539 SN - 1521-3765 VL - 21 IS - 20 SP - 7340 EP - 7344 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Klaper, Matthias A1 - Linker, Torsten T1 - New Singlet Oxygen Donors Based on Naphthalenes: Synthesis, Physical Chemical Data, and Improved Stability JF - Chemistry - a European journal N2 - Singlet oxygen donors are of current interest for medical applications, but suffer from a short half-life leading to low singlet oxygen yields and problems with storage. We have synthesized more than 25new singlet oxygen donors based on differently substituted naphthalenes in only a few steps. The influence of functional groups on the reaction rate of the photooxygenations, thermolysis, half-life, and singlet oxygen yield has been thoroughly studied. We determined various thermodynamic data and compared them with density functional calculations. Interestingly, remarkable stabilities of functional groups during the photooxygenations and stabilizing effects for some endoperoxides during the thermolysis have been found. Furthermore, we give evidence for a partly concerted and partly stepwise thermolysis mechanism leading to singlet and triplet oxygen, respectively. Our results might be interesting for dark oxygenations and future applications in medicine. KW - density functional calculations KW - oxygenation KW - peroxides KW - photodynamic therapy KW - singlet oxygen Y1 - 2015 U6 - https://doi.org/10.1002/chem.201500146 SN - 0947-6539 SN - 1521-3765 VL - 21 IS - 23 SP - 8569 EP - 8577 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Wang, Xuebin A1 - Wang, Xiaoli A1 - Hu, Jing A1 - Wang, Zhaoya A1 - Pimpalpalle, Tukaram M. A1 - Linker, Torsten A1 - Yin, Jian T1 - Study on the Synthesis of Novel Sugar Amino Acids T1 - 新型糖氨基酸类化合物的合成研究 JF - Acta chimica Sinica = Huaxue-xuebao N2 - Sugar amino acids (SAAs) are carbohydrate derivatives bearing both amino and carboxylic acid functional groups. SAAs represent an important class of multifunctional building blocks, which are amenable to serve as glycomimetics or peptidomimetics with well-defined structures and useful properties. Because SAAs exist in nature in many forms with various biological activities, recently, many unnatural SAAs, as the demand for finding new molecules to discover new drugs and new materials, have been designed and synthesized by a number of research groups. In this paper, we have developed a convenient method for the synthesis of novel SAAs gluco-7 and galacto-7 for the first time. The structure of gluco-7 was similar to the natural SAA glucosaminuronic acid that was a component of many typical bacterial cell walls and could be used for the preparation of type D flu vaccine; while galacto-7 was similar to the natural SAA galactosaminuronic acid that was one of bacterial Vi-antigen components of Escherichia coli. Starting from unexpensive and commercially available 3,4,6-tri-O-acetyl-D-glucal and 3,4,6-tri-O-acetyl-D-galactal, two novel SAAs gluco-7 and galacto-7 were achieved in the linear 6 steps with 34% overall yield and 19% overall yield, respectively. The key reactions included radical addition, decarboxylation, iodine generation reaction, azide reaction and reductive amination reaction. The crucial step was the synthesis of the target compound gluco-7 from gluco-6. By using method A, the target compound gluco-7 was obtained in 4 steps with 63% overall yield. To optimize the transformation from gluco-6 to gluco-7, method B was developed to generate gluco-7 by using one-pot reaction successfully with 76% yield only in one step. It proved that method B was superior to method A with shorter steps and higher yields. All the new compounds were characterized by IR, H-1 NMR, C-13 NMR and HRMS data. Study on the synthesis and biological evaluation of linear and cyclic oligomers derived from gluco-7 and galacto-7 are currently in progress. KW - sugar amino acids KW - glycal KW - radical addition KW - one-pot reaction KW - synthesis Y1 - 2015 U6 - https://doi.org/10.6023/A15030205 SN - 0567-7351 VL - 73 IS - 7 SP - 699 EP - 704 PB - Science China Press CY - Beijing ER - TY - JOUR A1 - Klaper, Matthias A1 - Linker, Torsten T1 - Intramolecular Transfer of Singlet Oxygen JF - Journal of the American Chemical Society N2 - The intramolecular transfer of energy (FRET) and electrons (Dexter) are of great interest for the scientific community and are well-understood. In contrast, the intramolecular transfer of singlet oxygen (O-1(2)), a reactive and short-lived oxygen species, has until now been unknown. This process would be very interesting because O-1(2) plays an important role in photodynamic therapy (PDT). Herein, we present the first successful intramolecular transfer of O-1(2) from a donor to acceptor. Also, we found a dependence of conformation and temperature comparable with those of FRET. We provide several pieces of evidence for the intramolecular character of this transfer, including competition experiments. Our studies should be interesting not only from the theoretical and mechanistic point of view but also for the design of new O-1(2) donors and applications in PDT. Y1 - 2015 U6 - https://doi.org/10.1021/jacs.5b07848 SN - 0002-7863 VL - 137 IS - 43 SP - 13744 EP - 13747 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Vankar, Yashwant D. A1 - Linker, Torsten T1 - Recent Developments in the Synthesis of 2-C-Branched and 1,2-Annulated Carbohydrates JF - European journal of organic chemistry N2 - The importance of carbohydrate chemistry in biological and medicinal chemistry has led to enormous developments in the synthesis of carbohydrate mimics. In this context, the synthesis of branched sugars in general and of 2-C-branched carbohydrates in particular, as well as the synthesis of 1,2-annulated sugars, have received immense attention. They serve not only as carbohydrate mimics in the form of stand-alone molecules, but also as useful intermediates in the synthesis of many natural products, their analogues, and glycosidase inhibitors. This microreview covers the recent synthetic efforts in this area and puts the subject matter into proper perspective for future developments. KW - Synthetic methods KW - Annulation KW - Carbohydrates KW - Carbohydrate mimics Y1 - 2015 U6 - https://doi.org/10.1002/ejoc.201501176 SN - 1434-193X SN - 1099-0690 IS - 35 SP - 7633 EP - 7642 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Fudickar, Werner A1 - Linker, Torsten T1 - Intermediates in the formation and thermolysis of peroxides from oxidations with singlet oxygen JF - Australian journal of chemistry N2 - Herein we describe the recent mechanistic understandings of the singlet oxygen ene reaction to give hydroperoxides and the [4+2] cycloaddition affording endoperoxides. Both experimental findings and theoretical work conclude in the formation of intermediates structurally similar to perepoxides during the ene reaction. Such intermediates mainly control the regio- and stereoselectivities of this reaction class. For the [4+2] cycloaddition, both a synchronous concerted reaction (benzene, naphthalenes) and a stepwise reaction with a non-symmetric zwitterionic intermediate (larger acenes) have been found. The thermolysis of endoperoxides derived from acenes proceeds stepwise for anthracenes, but in a concerted manner for less stable adducts such as naphthalene. Y1 - 2014 U6 - https://doi.org/10.1071/CH13423 SN - 0004-9425 SN - 1445-0038 VL - 67 IS - 3 SP - 320 EP - 327 PB - CSIRO CY - Clayton ER - TY - JOUR A1 - Pimpalpalle, Tukaram M. A1 - Vidadala, Srinivasa Rao A1 - Hotha, Srinivas A1 - Linker, Torsten T1 - Lewis acid-catalyzed stereoselective lactonization and subsequent glycosidation of 2-C-malonyl carbohydrates JF - Chemical communications N2 - Gold(III) bromide is a suitable catalyst for the stereoselective cyclization of 2-C-malonyl carbohydrates to the anomeric center under retention of one ester group. Reopening of the lactones with alcohols in the presence of TMSOTf affords allyl, propargyl and benzyl glycosides with high alpha-selectivity. Y1 - 2011 U6 - https://doi.org/10.1039/c1cc13425f SN - 1359-7345 VL - 47 IS - 37 SP - 10434 EP - 10436 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Yin, Jian A1 - Linker, Torsten T1 - Stereoselective diversity-oriented syntheses of functionalized saccharides from bicyclic carbohydrate 1,2-lactones JF - Tetrahedron N2 - Bicyclic carbohydrate 1,2-lactones have been synthesized in only two steps and high yields by saponification and subsequent cyclization from known malonate addition products to glycals. The gluco-configured lactone serves as an important precursor for diversity-oriented syntheses. Thus, stereoselective opening of the lactone ring was realized with various nucleophiles in the presence of Sc(OTf)(3). This enabled the introduction of different substituents at the anomeric position, to afford a broad variety of 1-functionalized carbohydrates. On the other hand, stereoselective alpha-substitution of the gluco-configured lactone with different electrophiles and subsequent ring opening gives a collection of 2-functionalized saccharides. More than 30 products have been isolated in analytically pure form, and their configurations were unequivocally established by various NMR methods. Thus, carbohydrate 1,2-lactones are attractive precursors for the stereoselective synthesis of diverse saccharides. KW - Carbohydrates KW - Lactones KW - Glycosides KW - Molecular diversity KW - Synthetic methods Y1 - 2011 U6 - https://doi.org/10.1016/j.tet.2011.01.069 SN - 0040-4020 VL - 67 IS - 13 SP - 2447 EP - 2461 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Vidadala, Srinivasa Rao A1 - Pimpalpalle, Tukaram M. A1 - Linker, Torsten A1 - Hotha, Srinivas T1 - Gold-Catalyzed reactions of 2-C-Branched carbohydrates mild glycosidations and selective anomerizations JF - European journal of organic chemistry N2 - 2-C-branched methyl glycosides react with various alcohols under gold catalysis to transglycosylated products. The method is applicable for the convenient synthesis of disaccharides. Without nucleophile a selective anomerization occurs, giving first access to alpha-configured 2-C-nitromethyl glycosides. The results are interesting for the mechanism of gold-catalyzed glycosidations. KW - Anomerization KW - Carbohydrates KW - Glycosidation KW - Gold KW - Synthetic methods Y1 - 2011 U6 - https://doi.org/10.1002/ejoc.201100134 SN - 1434-193X IS - 13 SP - 2426 EP - 2430 PB - Wiley-Blackwell CY - Malden ER - TY - JOUR A1 - Fudickar, Werner A1 - Linker, Torsten T1 - Reversible Photooxygenation of Alkynylanthracenes chemical generation of singlet oxygen under very mild conditions JF - Chemistry - a European journal KW - anthracenes KW - oxidation KW - peroxides KW - reversibility KW - singlet oxygen Y1 - 2011 U6 - https://doi.org/10.1002/chem.201102230 SN - 0947-6539 VL - 17 IS - 49 SP - 13661 EP - 13664 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Pimpalpalle, Tukaram M. A1 - Yin, Jian A1 - Linker, Torsten T1 - Barton radical reactions of 2-C-branched carbohydrates JF - Organic & biomolecular chemistry : an international journal of synthetic, physical and biomolecular organic chemistry N2 - Barton esters have been introduced into the side chain of carbohydrates with high yields in only a few steps from easily available glycals. Their radical reactions afford 2-C-methyl and 2-C-bromomethyl hexoses, pentoses and disaccharides in good yields in analytically pure form. Since the Barton esters have been synthesized by an oxidative radical addition and their transformations by reductive radical processes, our results demonstrate the power of such reactions in carbohydrate chemistry. Y1 - 2012 U6 - https://doi.org/10.1039/c1ob06370g SN - 1477-0520 VL - 10 IS - 1 SP - 103 EP - 109 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Yin, Jian A1 - Linker, Torsten T1 - Recent advances in the stereoselective synthesis of carbohydrate 2-C-analogs JF - Organic & biomolecular chemistry : an international journal of synthetic, physical and biomolecular organic chemistry N2 - C-branched carbohydrates are of current interest for glycochemistry, are widely found in nature and serve as important subunits in many antibiotics, bacterial polysaccharides and macrolides. Among C-functionalized saccharides, 2-C-branched carbohydrates represent challenging structures for synthetic chemists, since in contrast to C-glycosides they are not easily accessible from glycosyl bromides or other simple precursors. In this perspective we want to summarize recent approaches to 2-C-branched carbohydrates over the past fifteen years. The two main strategies are based on ring-opening of 1,2-cyclopropanated carbohydrates by various reagents, as well as radical additions to glycals and further transformations, developed in our group. Both methods are characterized by high stereoselectivities and good yields and give access to a broad variety of functionalized carbohydrate 2-C-analogs. Y1 - 2012 U6 - https://doi.org/10.1039/c2ob06529k SN - 1477-0520 VL - 10 IS - 12 SP - 2351 EP - 2362 PB - Royal Society of Chemistry CY - Cambridge 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 - Fudickar, Werner A1 - Linker, Torsten T1 - Why triple bonds protect acenes from oxidation and decomposition JF - Journal of the American Chemical Society N2 - An experimental and computational study on the impact of functional groups on the oxidation stability of higher acenes is presented. We synthesized anthracenes, tetracenes, and pentacenes with various substituents at the periphery, identified their photooxygenation products, and measured the kinetics. Furthermore, the products obtained from thermolysis and the kinetics of the thermolysis are investigated. Density functional theory is applied in order to predict reaction energies, frontier molecular orbital interactions, and radical stabilization energies. The combined results allow us to describe the mechanisms of the oxidations and the subsequent thermolysis. We found that the alkynyl group not only enhances the oxidation stability of acenes but also protects the resulting endoperoxides from thermal decomposition. Additionally, such substituents increase the regioselectivity of the photooxygenation of tetracenes and pentacenes. For the first time, we oxidized alkynylpentacenes by using chemically generated singlet oxygen (O-1(2)) without irradiation and identified a 6,13-endoperoxide as the sole regioisomer. The bimolecular rate constant of this oxidation amounts to only 1 X 10(5) s(-1) M-1. This unexpectedly slow reaction is a result of a physical deactivation of O-1(2). In contrast to unsubstituted or aryl-substituted acenes, photooxygenation of alkynyl-substituted acenes proceeds most likely by a concerted mechanism, while the thermolysis is well explained by the formation of radical intermediates. Our results should be important for the future design of oxidation stable acene-based semiconductors. Y1 - 2012 U6 - https://doi.org/10.1021/ja306056x SN - 0002-7863 VL - 134 IS - 36 SP - 15071 EP - 15082 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Bramborg, Andrea A1 - Linker, Torsten T1 - Regioselective synthesis of alkylarenes by two-step ipso-substitution of aromatic dicarboxylic acids JF - European journal of organic chemistry N2 - A strategy for the regioselective alkylation of arenes was developed, starting from commercially available and inexpensive terephthalic acid or naphthalene-1,4-dicarboxylic acid. The method entails a formal ipso-substitution of the carboxylate groups by a sequence of reductive alkylation under Birch conditions and subsequent acid-mediated rearomatization with loss of carbon monoxide and carbon dioxide. More than 20 different arenes with various side-chains were synthesized. With naphthalene-1,4-dicarboxylic acid as starting material, we were able to control the degree of alkylation by choosing the appropriate electrophile in the Birch reduction. Thus, bisalkylated naphthalenes and naphthoic acids became available chemoselectively. All reactions afforded a single regioisomer exclusively in high yields. Overall, aromatic dicarboxylic acids are suitable substrates for a two-step ipso-substitution that allows the selective synthesis of alkylated benzenes and naphthalenes. KW - Synthetic methods KW - Alkylation KW - Birch reduction KW - Arenes KW - Regioselectivity Y1 - 2012 U6 - https://doi.org/10.1002/ejoc.201200823 SN - 1434-193X IS - 28 SP - 5552 EP - 5563 PB - Wiley-VCH CY - Weinheim ER -