@misc{PapeWessigBrunner2015, author = {Pape, Simon and Wessig, Pablo and Brunner, Heiko}, title = {A new and environmentally benign synthesis of aroylguanidines using iron trichloride}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-102720}, pages = {101408 -- 101411}, year = {2015}, abstract = {A new synthetic approach for the guanylation of aroylthioureas using iron trichloride is presented. Our synthetic method distinguishes itself by benign reaction conditions, low costs and a broad product spectrum. The scope of the reaction and calorimetric studies are described.}, language = {en} } @article{SchildknechtPapeMeiseretal.2015, author = {Schildknecht, Stefan and Pape, Regina and Meiser, Johannes and Karreman, Christiaan and Strittmatter, Tobias and Odermatt, Meike and Cirri, Erica and Friemel, Anke and Ringwald, Markus and Pasquarelli, Noemi and Ferger, Boris and Brunner, Thomas and Marx, Andreas and Moeller, Heiko M. and Hiller, Karsten and Leist, Marcel}, title = {Preferential Extracellular Generation of the Active Parkinsonian Toxin MPP+ by Transporter-Independent Export of the Intermediate MPDP+}, series = {Antioxidants \& redox signaling}, volume = {23}, journal = {Antioxidants \& redox signaling}, number = {13}, publisher = {Liebert}, address = {New Rochelle}, issn = {1523-0864}, doi = {10.1089/ars.2015.6297}, pages = {1001 -- 1016}, year = {2015}, abstract = {Aims: 1-Methyl-4-phenyl-tetrahydropyridine (MPTP) is among the most widely used neurotoxins for inducing experimental parkinsonism. MPTP causes parkinsonian symptoms in mice, primates, and humans by killing a subpopulation of dopaminergic neurons. Extrapolations of data obtained using MPTP-based parkinsonism models to human disease are common; however, the precise mechanism by which MPTP is converted into its active neurotoxic metabolite, 1-methyl-4-phenyl-pyridinium (MPP+), has not been fully elucidated. In this study, we aimed to address two unanswered questions related to MPTP toxicology: (1) Why are MPTP-converting astrocytes largely spared from toxicity? (2) How does MPP+ reach the extracellular space? Results: In MPTP-treated astrocytes, we discovered that the membrane-impermeable MPP+, which is generally assumed to be formed inside astrocytes, is almost exclusively detected outside of these cells. Instead of a transporter-mediated export, we found that the intermediate, 1-methyl-4-phenyl-2,3-dihydropyridinium (MPDP+), and/or its uncharged conjugate base passively diffused across cell membranes and that MPP+ was formed predominately by the extracellular oxidation of MPDP+ into MPP+. This nonenzymatic extracellular conversion of MPDP+ was promoted by O-2, a more alkaline pH, and dopamine autoxidation products. Innovation and Conclusion: Our data indicate that MPTP metabolism is compartmentalized between intracellular and extracellular environments, explain the absence of toxicity in MPTP-converting astrocytes, and provide a rationale for the preferential formation of MPP+ in the extracellular space. The mechanism of transporter-independent extracellular MPP+ formation described here indicates that extracellular genesis of MPP+ from MPDP is a necessary prerequisite for the selective uptake of this toxin by catecholaminergic neurons.}, language = {en} } @article{PapeWessigBrunner2016, author = {Pape, Simon and Wessig, Pablo and Brunner, Heiko}, title = {Iron Trichloride and Air Mediated Guanylation of Acylthioureas. An Ecological Route to Acylguanidines: Scope and Mechanistic Insights}, series = {The journal of organic chemistry}, volume = {81}, journal = {The journal of organic chemistry}, publisher = {American Chemical Society}, address = {Washington}, issn = {0022-3263}, doi = {10.1021/acs.joc.6b00600}, pages = {4701 -- 4712}, year = {2016}, abstract = {Recently we introduced iron trichloride as an environmentally benign and cost-efficient reagent for the synthesis of N-benzoylguanidines. This highly attractive synthetic approach grants access to a broad spectrum of N-benzoylguanidines under mild conditions in short reaction times. In this work we present an extended scope of Our methodology along with the results obtained from mechanistic studies via in situ IR spectroscopy in combination with LC (liquid chromatography)-MS analyses. On the basis of these new mechanistic insights we were able to optimize the synthetic protocol and to develop an alternative mechanistic proposal. In this context the symbiotic roles of iron trithloride and oxygen in the guanylation process are highlighted.}, language = {en} } @article{SchmidtWolfBrunner2016, author = {Schmidt, Bernd and Wolf, Felix and Brunner, Heiko}, title = {Styrylsulfonates and -Sulfonamides through Pd-Catalysed Matsuda-Heck Reactions of Vinylsulfonic Acid Derivatives and Arenediazonium Salts}, series = {European journal of organic chemistry}, journal = {European journal of organic chemistry}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1434-193X}, doi = {10.1002/ejoc.201600469}, pages = {2972 -- 2982}, year = {2016}, abstract = {Arene diazonium salts undergo Matsuda-Heck reactions with vinylsulfonates and -sulfonamides to give styrylsulfonic acid derivatives in high to excellent yields and with high to excellent selectivities. By quantifying the evolution of nitrogen over time in a gas-meter apparatus, the reactivities of ethylvinylsulfonate and the benchmark olefin methyl acrylate were compared for an electron-rich and an -deficient arene diazonium salt. Tertiary sulfonamides react in Matsuda-Heck couplings with high conversions, but require long reaction times, which prevents the determination of kinetic data through the measurement of nitrogen evolution. Secondary sulfonamides were found to be unreactive. From these results, the following order of reactivity could be deduced: H2C=CHCO2Me > H2C=CHSO2OEt > H2C=CHSO2N(Me)Bn >> H2C=CHSO2NHBn. Through the Matsuda-Heck coupling of 5-indolyldiazonium salt and a tertiary vinylsulfonamide, the synthesis of the C-5-substituted indole part of the antimigraine drug naratriptan was accomplished in high yield.}, language = {en} } @article{PapeWessigBrunner2015, author = {Pape, Simon and Wessig, Pablo and Brunner, Heiko}, title = {A new and environmentally benign synthesis of aroylguanidines using iron trichloride}, series = {RSC Advances}, volume = {5}, journal = {RSC Advances}, number = {123}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {2046-2069}, doi = {10.1039/c5ra20869f}, pages = {101408 -- 101411}, year = {2015}, abstract = {A new synthetic approach for the guanylation of aroylthioureas using iron trichloride is presented. Our synthetic method distinguishes itself by benign reaction conditions, low costs and a broad product spectrum. The scope of the reaction and calorimetric studies are described.}, language = {en} }