Research

Our research is focused on the development and application of elegant and efficient synthetic and catalytic methods, on carbohydrates and glycolipids and on fluorescent dyes.

Donor-Acceptor-Cyclopropanes

The weak bond between vicinal donors and acceptors in a cyclopropane paves the way for a plethora of unusual reactions. Guided by quantum chemical studies1 we designed methods to obtain oligoacetals2,3 and spiroketals4 starting from respective cyclopropanes. These results were the basis to develop also routes from furan to 3,3‘-linked bispyrrols and larger oligomers.5 Similar transformations employing chalcogen-transferring agents yielded 3,3‘-linked bisthiophenes or corresponding cage-like compounds.6

[1] T. F. Schneider, D. B. Werz, Org. Lett. 2011, 13, 1848-1851.
[2] T. F. Schneider, J. Kaschel, B. Dittrich, D. B. Werz, Org. Lett. 2009, 11, 2317-2320.
[3] T. F. Schneider, J. Kaschel, S. I. Awan, B. Dittrich, D. B. Werz, Chem. Eur. J. 2010, 16, 11276-11288.
[4] C. Brand, G. Rauch, M. Zanoni, B. Dittrich, D. B. Werz, J. Org. Chem. 2009, 74, 8779-8786.
[5] J. Kaschel, T. F. Schneider, D. Kratzert, D. Stalke, D. B. Werz, Angew. Chem. Int. Ed. 2012, 51, 11153-11156.
[6] J. Kaschel, C. D. Schmidt, M. Mumby, D. Kratzert, D. Stalke, D. B. Werz, Chem. Commun. 2013, 49, 4403-4405.

Carbopalladations Cascades

Highly efficient Pd-catalyzed domino sequences are applied for the synthesis of chromans and isochromans starting from carbohydrates.7,8 In such a way, stereochemical information of the carbohydrate is transferred to the heterocyclic system. Similarly, persubstituted biphenyls are generated in one step.9 Related sequences starting with appropriately substituted arenes furnish interesting π systems in a short and efficient manner,10 e.g. dibenzopentafulvalenes were accessed by a quadruple domino carbopalladation sequence.11

[7] M. Leibeling, D. C. Koester, M. Pawliczek, S. C. Schild, D. B. Werz, Nature Chem. Biol. 2010, 6, 199-201.
[8] M. Leibeling, B. Milde, D. Kratzert, D. Stalke, D. B. Werz, Chem. Eur. J. 2011, 17, 9888-9892.
[9] M. Leibeling, D. B. Werz, Chem. Eur. J. 2012, 18, 6138-6141.
[10] M. Leibeling, M. Pawliczek, D. Kratzert, D. Stalke, D. B. Werz, Org. Lett. 2012, 14, 346-349.
[11] J. Wallbaum, R. Neufeld, D. Stalke, D. B. Werz, Angew. Chem. Int. Ed. 2013, 52, 13243-13246.

Carbohydrate and Glycolipid Chemistry

In the field of carbohydrate chemistry the WERZ research group is active in the preparation and biological evaluation of bacterial carbohydrates as well as mammalian glycolipids. Different questions (sometimes studied in collaboration) are in the focus.
As part of the Collaborative Research Center (SFB 803) on membranes we are interested in the tailor-made assembly of glycosphingolipids with variable hydrocarbon chains by using a modular chemical approach. Next to their biological relevance a major aim of this project is to get insights into the fundamental processes of membrane domain formation.12 The use of a new class of fluorescent dyes13 with minimal impact on the structural integrity of membrane domains allows the visualization of lateral organization and fate of membrane structures in transport processes and fusion assays of glycolipid-rich membranes.
In collaboration with biophysicists force constants between single oligosaccharides derived from the marine sponge Microciona prolifera were measured and served as model systems for multivalent interactions in early evolutionary stages of life.14

[12] O. M. Schütte, A. Ries, A. Orth, L. J. Patalag, W. Römer, C. Steinem, D. B. Werz, Chem. Sci. 2014, 5, 3104-3114.
[13] L. J. Patalag, D. B. Werz, J. Org. Chem. 2012, 77, 5297-5304.
[14] A. de Cienfuegos, M. Oelkers, E. Kriemen, C. Brand, M. Stephan, E. Sunnick, D. Yüksel, V. Kalsani, K. Kumar, D. B. Werz, A. Janshoff, J. Am. Chem. Soc. 2012, 134, 3326-3329.

Carbohydrate Mimics

Next to O-glycoside chemistry we are also involved in the synthesis of C-glycosides using a highly modular approach.15 In contrast to O-glycosidic bonds C-glycosidic bonds are not cleaved by hydrolysis or enzymolysis. Key reactions we use in our strategy are Pd-catalyzed coupling reactions allowing the efficient preparation of C-glycosidic bonds between different monosaccharide building blocks. Especially Pd-catalyzed Sonogashira and Stille reactions of alkynes or olefins in combination with 1-functionalized glycals were utilized. In a further step the native hydroxyl pattern is regenerated.16

Spiroannelated cyclopropanes are another possibility to influence conformations of saccharides. We developed synthetic routes to attach a spiroannelated three-membered ring at the C-5 position.17,18 On one hand side, the inversion of the pyran ring is hampered, on the other the 6-hydroxyl group is precisely located to either the left or the right side of the cyclopropane. The attachment of the cyclopropyl subunit is the smallest possible modification, the structural integrity of the pyran is almost maintained.

[15] D. C. Koester, A. Holkenbrink, D. B. Werz, Synthesis 2010, 3217-3242.
[16] D. C. Koester, E. Kriemen, D. B. Werz, Angew. Chem. Int. Ed. 2013, 52, 3059-3063.
[17] C. Brand, M. Granitzka, D. Stalke, D. B. Werz, Chem. Commun. 2011, 47, 10782-10784.
[18] C. Brand, K. Kettelhoit, D. B. Werz, Org. Lett. 2012, 14, 5126-5129.

Novel Types of Fluorescent Dyes

Inspired by the well-known BODIPY motif a fast entry into a novel family of highly fluorescent fluorophores termed BOIMPYs was designed. Two BF2 units ensure an efficient exploitation of the meso position and trigger absorptions at ~ 600 nm. The structural relationship to well-studied BODIPYs enables common modes of post-functionalization to be easily transferable to the new motif.19

[19] L. J. Patalag, P. G. Jones, D. B. Werz, Angew. Chem. Int. Ed. 2016, 55, 13340-13344.

TU Braunschweig
Institut für Organische Chemie
Hagenring 30
D-38106 Braunschweig
Phone: +49-(0)531-391 5266
Fax: +49-(0)531-391 5272
d.werz@tu-braunschweig.de
www.werzlab.de
Last updated:
November-17-2017