Co-reporter:Vanessa Koch;Stefan Bräse
Organic & Biomolecular Chemistry 2017 vol. 15(Issue 1) pp:92-95
Publication Date(Web):2016/12/20
DOI:10.1039/C6OB02496C
Herein, we report on Pd-mediated cross-coupling of vinyllithium steroids and aryl bromides to introduce various substituted aryls at C-17 of steroidal frameworks based on the structure of epi-androsterone. Compared to other C–C cross-couplings, this method turned out to be an easy and competitive access to biologically interesting C-17 modified steroids.
Co-reporter:Nils Griebenow, Alicia M. Dilmaç, Simone Greven, and Stefan Bräse
Bioconjugate Chemistry 2016 Volume 27(Issue 4) pp:911
Publication Date(Web):March 31, 2016
DOI:10.1021/acs.bioconjchem.5b00682
Herein, we describe an extension of our previously reported photomediated disulfide rebridging methodology to the conjugation of peptides and proteins. The methodology proved to be reproducible with various alkynes and different peptides. This study includes the first rebridging of the disulfide bond of a peptide through a thiol–yne reaction with a cyclooctyne. In all cases, the rebridging was proven by MS analyses and confirmed by the absence of olefinic protons on 1H NMR spectra of the resulting products. Finally, this one-pot reduction thiol–yne conjugation was successfully applied to an antibody Fab fragment with a promising conversion, which set a good ground for the future syntheses of new protein and antibody conjugates.
Co-reporter:Sylvestre P. J. T. Bachollet;Dr. Daniel Volz;Béla Fiser;Stephan Münch;Dr. Franziska Rönicke;Dr. Jokin Carrillo;Harry Adams; Ute Schepers;Enrique Gómez-Bengoa; Stefan Bräse; Joseph P. A. Harrity
Chemistry - A European Journal 2016 Volume 22( Issue 35) pp:12430-12438
Publication Date(Web):
DOI:10.1002/chem.201601915
Abstract
Ten borylated bipyridines (BOBIPYs) have been synthesized and selected structural modifications have been made that allow useful structure–optical property relationships to be gathered. These systems have been further investigated using DFT calculations and spectroscopic measurements, showing blue to green fluorescence with quantum yields up to 41 %. They allow full mapping of the structure to determine where selected functionalities can be implemented, to tune the optical properties or to incorporate linking groups. The best derivative was thus functionalised with an alkyne linker, which would enable further applications through click chemistry and in this optic, the stability of the fluorophores has been evaluated.
Co-reporter:Konstantin V. Kudryavtsev, Polina M. Ivantcova, Claudia Muhle-Goll, Andrei V. Churakov, Mikhail N. Sokolov, Artem V. Dyuba, Alexander M. Arutyunyan, Judith A. K. Howard, Chia-Chun Yu, Jih-Hwa Guh, Nikolay S. Zefirov, and Stefan Bräse
Organic Letters 2015 Volume 17(Issue 24) pp:6178-6181
Publication Date(Web):December 1, 2015
DOI:10.1021/acs.orglett.5b03154
To produce a novel class of structurally ordered poly-β-prolines, an emergent method for synthesizing chiral β-peptide molecular frameworks was developed based on 1,3-dipolar cycloaddition chemistry of azomethine ylides. Functionalized short β-peptides with up to six monomeric residues were efficiently synthesized in homochiral forms using a cycloadditive oligomerization approach. X-ray, NMR, and CD structural analyses of the novel β-peptides revealed secondary structure features that were generated primarily by Z/E-β-peptide bond isomerism. Anticancer in cellulo activity of the new β-peptides toward hormone-refractory prostate cancer cells was observed and was dependent on the absolute configuration of the stereogenic centers and the chain length of the β-proline oligomers.
Co-reporter:Meike A. Gotthardt, Sylvain Grosjean, Tobias S. Brunner, Johannes Kotzel, Andreas M. Gänzler, Silke Wolf, Stefan Bräse and Wolfgang Kleist
Dalton Transactions 2015 vol. 44(Issue 38) pp:16802-16809
Publication Date(Web):24 Aug 2015
DOI:10.1039/C5DT02276B
Functionalized 4,4′-biphenyldicarboxylic acid molecules with additional amine, alkyne, azide or nitro groups were prepared and applied in the synthesis of novel metal–organic frameworks and mixed-linker metal–organic frameworks isoreticular to DUT-5. The properties of the frameworks could be tuned by varying the number of functional groups in the materials and the amine groups were employed in post-synthetic modification reactions without changing the framework structure or significantly decreasing the porosity of the materials.
Co-reporter:Nils Griebenow, Simone Greven, Mario Lobell, Alicia M. Dilmaç and Stefan Bräse
RSC Advances 2015 vol. 5(Issue 125) pp:103506-103511
Publication Date(Web):24 Nov 2015
DOI:10.1039/C5RA18271A
Herein, we report on the conjugation of trastuzumab with 2,5-difluorobenzene diazonium tetrafluoroborate. According to the amount of diazonium salt used, an average loading of 1.0 to 3.8 azo compounds per antibody was found. Tryptic digestion and subsequent MS–MS analyses allowed the identification of the main conjugation sites. Furthermore, additional conjugation reactions of trastuzumab with 4-formylbenzene diazonium hexafluorophosphate (FBDP) allows us to make a short study on the influence of the different reaction parameters on the outcome of the conjugation reaction, both in terms of antibody loading and of conjugation sites. In all cases, antibody conjugation was achieved with full selectivity towards tyrosine residues.
Co-reporter:Dr. Sabilla Zhong;Paul F. Sauter;Dr. Martin Nieger;Dr. Stefan Bräse
Chemistry - A European Journal 2015 Volume 21( Issue 31) pp:11219-11225
Publication Date(Web):
DOI:10.1002/chem.201501199
Abstract
The stereoselective synthesis of a variety of functionalized hydroindoles suitable as building blocks for thiodiketopiperazine natural products such as rostratins B–D is reported. The key precursor for all transformations is a previously reported hexahydroindole compound. All functional groups were installed with the desired stereochemistry and the feasibility of the synthetic strategy was exemplified by dimerization of two hydroindole units to form the pentacyclic C2-symmetric scaffold of rostratin C.
Co-reporter:Nicole Jung, Bettina Stanek, Simone Gräßle, Martin Nieger, and Stefan Bräse
Organic Letters 2014 Volume 16(Issue 4) pp:1112-1115
Publication Date(Web):February 11, 2014
DOI:10.1021/ol4037133
The conversion of dithianylium cations into α-azo ketene dithioacetals via addition of polymer-bound diazonium precursors is shown. This new procedure allows the synthesis of α-azo ketene dithioacetals in one step within 2–90 min at rt and yields highly pure compounds that do not have to be purified in most cases. The α-azo ketene dithioacetals obtained have been shown to be valuable intermediates for the synthesis of hydrazones, α-halogenated α-azo ketene dithioacetals, and azo-functionalized dienes.
Co-reporter:N. Jung, S. Grässle, D. S. Lütjohann, and S. Bräse
Organic Letters 2014 Volume 16(Issue 4) pp:1036-1039
Publication Date(Web):January 31, 2014
DOI:10.1021/ol403313h
A solid supported, odorless reagent for the dithioacetalization of aldehydes and ketones has been developed. The new reagent provides the dimercaptoalkane equivalent in combination with stoichiometric amounts of immobilized acid and enables the formation of dithianes and dithiolanes from aldehydes without any additives in good to very good yields with high purities. The reaction is chemoselective for aldehydes, but ketones can be reacted to the corresponding dithioketals if an additional Lewis acid such as BF3 is added.
Co-reporter:Anna Hörner, Daniel Volz, Tobias Hagendorn, Daniel Fürniss, Lutz Greb, Franziska Rönicke, Martin Nieger, Ute Schepers and Stefan Bräse
RSC Advances 2014 vol. 4(Issue 23) pp:11528-11534
Publication Date(Web):06 Feb 2014
DOI:10.1039/C3RA47964A
Imaging is – even these days – still restricted to of a few classes of robust dyes. A demand for switchable tags led us to the design of a new class of pre-fluorophores. We achieved this by using a non-fluorescent N-(4-azidophenyl)-carbazole tag which turns fluorescent by click reaction with alkynes and cyclooctynes. The spectral properties of the labelled dyes were investigated. Our results suggest that a twisted internal charge transfer (TICT) transition is responsible for the emission. DFT calculations and single-crystal X-ray diffraction of selected examples support this explanation. The feasibility of the new dyes for biological application has also been tested via confocal microscopy.
Co-reporter:Tobias Hagendorn and Stefan Bräse
RSC Advances 2014 vol. 4(Issue 30) pp:15493-15495
Publication Date(Web):19 Mar 2014
DOI:10.1039/C4RA01345J
The current paper describes a new synthesis of heteroatom-substituted cyclooctynes. By using the Nicholas reaction we managed to design a concise synthesis that only uses three steps to build the eight-membered ring. It was also possible to functionalize said alkyne with a fluorophore.
Co-reporter:Mark Busch;Merve Cayir;Martin Nieger;Werner R. Thiel;Stefan Bräse
European Journal of Organic Chemistry 2013 Volume 2013( Issue 27) pp:6108-6123
Publication Date(Web):
DOI:10.1002/ejoc.201300508
Abstract
A novel family of [2.2]paracyclophane derivatives is described. Different substituted pyrazole, triazole and pyrimidine moieties were introduced to the [2.2]paracyclophane scaffold and the products were characterized spectroscopically and by X-ray structure analysis. These compounds are promising ligands for application in asymmetric catalysis. We show here that one of these ligands can catalyze asymmetric conjugate addition. Furthermore a palladium complex was synthesized by using a hydroxy-pyrazolyl[2.2]paracyclophane ligand.
Co-reporter:Dr. Kye-Simeon Masters ;Dr. Angela Bihlmeier;Dr. Wim Klopper;Dr. Stefan Bräse
Chemistry - A European Journal 2013 Volume 19( Issue 52) pp:17827-17835
Publication Date(Web):
DOI:10.1002/chem.201301969
Abstract
2,2'-Biphenols are a large and diverse group of compounds with exceptional properties both as ligands and bioactive agents. Traditional methods for their synthesis by oxidative dimerisation are often problematic and lead to mixtures of ortho- and para-connected regioisomers. To compound these issues, an intermolecular dimerisation strategy is often inappropriate for the synthesis of heterodimers. The ‘acetal method’ provides a solution for these problems: stepwise tethering of two monomeric phenols enables heterodimer synthesis, enforces ortho regioselectivity and allows relatively facile and selective intramolecular reactions to take place. The resulting dibenzo[1,3]dioxepines have been analysed by quantum chemical calculations to obtain information about the activation barrier for ring flip between the enantiomers. Hydrolytic removal of the dioxepine acetal unit revealed the 2,2′-biphenol target.
Co-reporter:Dr. Kye-Simeon Masters;Dr. Stefan Bräse
Angewandte Chemie International Edition 2013 Volume 52( Issue 3) pp:866-869
Publication Date(Web):
DOI:10.1002/anie.201207485
Co-reporter:Carl F. Nising and Stefan Bräse
Chemical Society Reviews 2012 vol. 41(Issue 3) pp:988-999
Publication Date(Web):28 Jul 2011
DOI:10.1039/C1CS15167C
Oxa-Michael reactions, i.e. addition reactions of oxygen nucleophiles to conjugated systems, have traditionally received much less attention from the scientific community compared to the addition of carbon nucleophiles to conjugate acceptor systems (Michael reaction). This was mainly due to lack of reactivity and selectivity of these reactions. Within the last few years however, there has been a remarkable increase in publications focussing on method development as well as applications to natural product synthesis. This tutorial review discusses instructive examples that have substantially broadened the scope of oxa-Michael reactions.
Co-reporter:Ozcan Altintas;Thierry Muller;Elise Lejeune;Oliver Plietzsch;Stefan Bräse;Christopher Barner-Kowollik
Macromolecular Rapid Communications 2012 Volume 33( Issue 11) pp:977-983
Publication Date(Web):
DOI:10.1002/marc.201200019
Abstract
A well-defined random copolymer of styrene (S) and chloromethylstyrene (CMS) featuring lateral chlorine moieties with an alkyne terminal group is prepared (P(S-co-CMS), = 5500 Da, PDI = 1.13). The chloromethyl groups are converted into Hamilton wedge (HW) entities (P(S-co-HWS), = 6200 Da, PDI = 1.13). The P(S-co-HWS) polymer is subsequently ligated with tetrakis(4-azidophenyl)methane to give HW-functional star-shaped macromolecules (P(S-co-HWS))4, = 25 100 Da, PDI = 1.08). Supramolecular star-shaped copolymers are then prepared via self-assembly between the HW-functionalized four-arm star-shaped macromolecules (P(S-co-HW))4 and cyanuric acid (CA) end-functionalized PS (PS–CA, = 3700 Da, PDI = 1.04), CA end-functionalized poly(methyl methacrylate) (PMMA–CA, = 8500 Da, PDI = 1.13) and CA end-functionalized polyethylene glycol (PEG–CA, = 1700 Da, PDI = 1.05). The self-assembly is monitored by 1H NMR spectroscopy and light scattering analyses.
Co-reporter:Ozcan Altintas;Thierry Muller;Elise Lejeune;Oliver Plietzsch;Stefan Bräse;Christopher Barner-Kowollik
Macromolecular Rapid Communications 2012 Volume 33( Issue 11) pp:
Publication Date(Web):
DOI:10.1002/marc.201290036
Co-reporter:Daniel Fürniss, Ute Schepers and Stefan Bräse
RSC Advances 2012 vol. 2(Issue 30) pp:11273-11278
Publication Date(Web):19 Sep 2012
DOI:10.1039/C2RA22189F
Alkenes can be reduced through “transfer hydrogenation” with dimethylamine-borane adduct and Wilkinson's catalyst. This reaction can also be carried out by solid-phase synthesis as a heterogeneous reaction. Furthermore, the behaviour of various functional groups under hydrogenation conditions was tested.
Co-reporter:Anne J. Rüger, Martin Nieger, Stefan Bräse
Tetrahedron 2012 68(42) pp: 8823-8829
Publication Date(Web):
DOI:10.1016/j.tet.2012.07.069
Co-reporter:Dagmar C. Kapeller and Stefan Bräse
ACS Combinatorial Science 2011 Volume 13(Issue 5) pp:554
Publication Date(Web):August 4, 2011
DOI:10.1021/co200107s
A novel solid-phase approach toward classical cannabinoids is described. The desired tricyclic natural product analogues are assembled in only four atom economic steps: domino oxa-Michael-aldol condensation, Wittig reaction/enol-ether formation, Diels–Alder cycloaddition and cleavage. The synthesis is designed to allow combinatorial chemistry at several stages of the sequence. The variation of commercially available reagents at three of the reactions (enals/enones, Wittig salts, and dienophiles) allows the introduction of various diversity points. As proof of concept, a small library of 20 members has been synthesized with overall yields ranging from 10% to 60%.Keywords: cannabinoids; combinatorial chemistry; domino reactions; heterocycles; natural products; solid phase synthesis
Co-reporter:Anna M. Linsenmeier, Craig M. Williams, and Stefan Bräse
The Journal of Organic Chemistry 2011 Volume 76(Issue 21) pp:9127-9132
Publication Date(Web):September 21, 2011
DOI:10.1021/jo201542x
An improved photochemical method for producing the prolifically bioactive phenanthridine system is reported. A wide variety of derivatives were obtained in two steps in yields ranging from 31 to 95%.
Co-reporter:Rüdiger Reingruber;Thomas Baumann;Stefan Dahmen;Stefan Bräse
Advanced Synthesis & Catalysis 2009 Volume 351( Issue 7-8) pp:1019-1024
Publication Date(Web):
DOI:10.1002/adsc.200800798
Co-reporter:Caroline E. Hartmann, Patrick J. Gross, Martin Nieger and Stefan Bräse
Organic & Biomolecular Chemistry 2009 vol. 7(Issue 24) pp:5059-5062
Publication Date(Web):19 Oct 2009
DOI:10.1039/B916372G
Studies towards the synthesis of the bacterial peptide deformylase (PDF) inhibitor fumimycin are reported. The synthetic approach features an organocatalytic access to the α,α-disubstituted amino acid unit and results in the synthesis of an advanced intermediate which already contains all functionalities of fumimycin.
Co-reporter:Oliver Plietzsch, Christine Inge Schilling, Mariyan Tolev, Martin Nieger, Clemens Richert, Thierry Muller and Stefan Bräse
Organic & Biomolecular Chemistry 2009 vol. 7(Issue 22) pp:4734-4743
Publication Date(Web):14 Sep 2009
DOI:10.1039/B912189G
A modular concept for the generation of achiral and chiral non-racemic tetrahedral tectons from common precursors was developed. The tectons presented here are based on tetraphenylmethane or 1,3,5,7-tetraphenyladamantane core structures. They are obtained through high-yielding four-fold click reactions, using either the tetraazido or the tetraalkyne precursors. In most cases, the tetratriazoles are obtained as pure products after simple washing with water and methanol. The side chains of the tectons prepared include a self-complementary DNA dimer, obtained from a 3′-azidonucleoside and a phosphoramidite. The concept allows for a variation of the “sticky ends”, leading to tecton or ligand libraries.
Co-reporter:Philippe Pierrat Dr.;Céline Réthoré Dr.;Thierry Muller Dr. ;Stefan Bräse Dr.
Chemistry - A European Journal 2009 Volume 15( Issue 43) pp:11458-11460
Publication Date(Web):
DOI:10.1002/chem.200902141
Co-reporter:Rüdiger Reingruber, Sylvia Vanderheiden, Thierry Muller, Martin Nieger, Mazen Es-Sayed, Stefan Bräse
Tetrahedron Letters 2009 50(26) pp: 3439-3442
Publication Date(Web):
DOI:10.1016/j.tetlet.2009.02.184
Co-reporter:Caroline E. Hartmann, Patrick J. Gross, Martin Nieger and Stefan Bräse
Organic & Biomolecular Chemistry 2009 - vol. 7(Issue 24) pp:NaN5062-5062
Publication Date(Web):2009/10/19
DOI:10.1039/B916372G
Studies towards the synthesis of the bacterial peptide deformylase (PDF) inhibitor fumimycin are reported. The synthetic approach features an organocatalytic access to the α,α-disubstituted amino acid unit and results in the synthesis of an advanced intermediate which already contains all functionalities of fumimycin.
Co-reporter:Oliver Plietzsch, Christine Inge Schilling, Mariyan Tolev, Martin Nieger, Clemens Richert, Thierry Muller and Stefan Bräse
Organic & Biomolecular Chemistry 2009 - vol. 7(Issue 22) pp:NaN4743-4743
Publication Date(Web):2009/09/14
DOI:10.1039/B912189G
A modular concept for the generation of achiral and chiral non-racemic tetrahedral tectons from common precursors was developed. The tectons presented here are based on tetraphenylmethane or 1,3,5,7-tetraphenyladamantane core structures. They are obtained through high-yielding four-fold click reactions, using either the tetraazido or the tetraalkyne precursors. In most cases, the tetratriazoles are obtained as pure products after simple washing with water and methanol. The side chains of the tectons prepared include a self-complementary DNA dimer, obtained from a 3′-azidonucleoside and a phosphoramidite. The concept allows for a variation of the “sticky ends”, leading to tecton or ligand libraries.
Co-reporter:Carl F. Nising and Stefan Bräse
Chemical Society Reviews 2012 - vol. 41(Issue 3) pp:NaN999-999
Publication Date(Web):2011/07/28
DOI:10.1039/C1CS15167C
Oxa-Michael reactions, i.e. addition reactions of oxygen nucleophiles to conjugated systems, have traditionally received much less attention from the scientific community compared to the addition of carbon nucleophiles to conjugate acceptor systems (Michael reaction). This was mainly due to lack of reactivity and selectivity of these reactions. Within the last few years however, there has been a remarkable increase in publications focussing on method development as well as applications to natural product synthesis. This tutorial review discusses instructive examples that have substantially broadened the scope of oxa-Michael reactions.
Co-reporter:Meike A. Gotthardt, Sylvain Grosjean, Tobias S. Brunner, Johannes Kotzel, Andreas M. Gänzler, Silke Wolf, Stefan Bräse and Wolfgang Kleist
Dalton Transactions 2015 - vol. 44(Issue 38) pp:NaN16809-16809
Publication Date(Web):2015/08/24
DOI:10.1039/C5DT02276B
Functionalized 4,4′-biphenyldicarboxylic acid molecules with additional amine, alkyne, azide or nitro groups were prepared and applied in the synthesis of novel metal–organic frameworks and mixed-linker metal–organic frameworks isoreticular to DUT-5. The properties of the frameworks could be tuned by varying the number of functional groups in the materials and the amine groups were employed in post-synthetic modification reactions without changing the framework structure or significantly decreasing the porosity of the materials.
Co-reporter:Vanessa Koch and Stefan Bräse
Organic & Biomolecular Chemistry 2017 - vol. 15(Issue 1) pp:NaN95-95
Publication Date(Web):2016/11/22
DOI:10.1039/C6OB02496C
Herein, we report on Pd-mediated cross-coupling of vinyllithium steroids and aryl bromides to introduce various substituted aryls at C-17 of steroidal frameworks based on the structure of epi-androsterone. Compared to other C–C cross-couplings, this method turned out to be an easy and competitive access to biologically interesting C-17 modified steroids.