Research groups
Kirschning group

Research Group Prof. Dr. Andreas Kirschning

Synthetic chemistry

Our research group provides a home for Synthetic Chemistry in a broad sense. We utilize and combine chemistry, biotechnology and synthetic enabling technologies for drug-oriented natural product research and the development of smart biomedical materials.

Synthetic chemistry

Our research group provides a home for Synthetic Chemistry in a broad sense. We utilize and combine chemistry, biotechnology and synthetic enabling technologies for drug-oriented natural product research and the development of smart biomedical materials.

Our research topics

The ability to design and synthesize new molecules, and to explore their molecular architectures, is a tool of enormous power that has facilitated the development of many areas within the field of molecular science. Research in the Kirschning group aims to strategically combine a diverse range of these synthetic approaches, including biotechnological methods based on enzymes and whole cells; enabling technologies such as flow chemistry and inductive heating in organic synthesis; and the total synthesis of complex organic molecules, to initiate biomedical studies of new molecules and materials with promising therapeutic potential.

BioMed: Biomedical materials

Polysaccharide-based hydrogels – a versatile toolbox for tissue engineering

We developed a synthetic tool box for functionalizing polysaccharides (hyaluronic acid, alginate, dextran, pullulan, glycogen, lentinan and carboxymethyl cellulose) with “clickable” aldehydo and hydrazido groups. They allow in vivo hydrogel formation upon mixing.
Furthermore, functionalization of clickable polysaccharide strands with bioactive ligands such as cyclic RGD pentapeptides as cell adhesion factors has been achieved in an orthogonal manner. In that way libraries of polysaccharide-based hydrogels were created including those that are based on different polysaccharide backbones.
These studies are complemented with studies on their biophysical properties, biocompatibility and biodegradability as well as substitutes for extracellular matrices.

  • Publications
    • Kirschning, A., Dibbert, N., & Dräger, G. (2017). Chemical Functionalization of Polysaccharides: Towards Biocompatible Hydrogels for Biomedical Applications. Chemistry - A European Journal, 24(6), 1231-1240.

    • Dahlmann, J., Kensah, G., Kempf, H., Skvorc, D., Gawol, A., Elliott, D. A., Dräger, G., Zweigerdt, R., Martin, U., & Gruh, I. (2013). The use of agarose microwells for scalable embryoid body formation and cardiac differentiation of human and murine pluripotent stem cells. BIOMATERIALS, 34(10), 2463-2471.
    • Möller, L., Krause, A., Dahlmann, J., Gruh, I., Kirschning, A., & Dräger, G. (2011). Preparation and evaluation of hydrogel-composites from methacrylated hyaluronic acid, alginate, and gelatin for tissue engineering. International Journal of Artificial Organs, 34(2), 93-102.
    • Dibbert, N., Krause, A., Rios-Camacho, J. C., Gruh, I., Kirschning, A., & Dräger, G. (2016). A Synthetic Toolbox for the In Situ Formation of Functionalized Homo- and Heteropolysaccharide-Based Hydrogel Libraries. Chemistry - A European Journal, 22(52), 18777-18786.

Biocompatible artifical lung

The biomedical problem: Respiratory failures are a significant health-care problem with several hundred thousand adult patients each year. The use of mechanical oxygenators (left) that provide breathing support while the recovery of the lungs occurs, is often indispensable. Extracorporeal devices are based on polymeric hollow fiber membranes (central), that serve as interface between blood and gas streams. In order to improve the biomedical properties and prevent blocking, endothelial cells (ECs) can be seeded onto the membrane surface (right). Nevertheless the cells show only low surface adhesion, which must be improved by attaching adhesion factors such as cyclic RGD peptide.

The chemical solution: Covalent multi-step coating of polymethylpentene (oxygen plasma, nitrene insertion, PEG coupling and copper-free click coupling of RGD) provided a highly biocompatible polymer surface. The resulting modified membrane preserves the required excellent gas flow properties while being densely seeded with endothelial cells.

  • Publications
    • Möller, L., Hess, C., Paleček, J., Su, Y., Haverich, A., Kirschning, A., & Dräger, G. (2013). Towards a biocompatible artificial lung: Covalent functionalization of poly(4-methylpent-1-ene) (TPX) with cRGD pentapeptide. Beilstein Journal of Organic Chemistry, 9, 270-277.

SynBio: Biotransformations

Mutasynthesis: a synthetic tool in natural product chemistry

The ansamitocins (maytansinoids), geldanamycin as well as rifamycin are famous members of the class of ansamycin antibiotics which all bear aminohydroxybenzoic acid (AHBA) as polyketide synthase (PKS) starting building block.

Mutasynthesis is a straightforward technique, that combines the genetic manipulation of biosynthetic pathways with chemical synthesis. It requires the generation of mutants of a producer organism blocked in the formation of a biosynthetic building block of the end-product. Administration of structurally modified, so called mutasynthons to these blocked mutant reconstitutes the substrate flow. However, in these cases the structural modifications result in new metabolites.

We carried out comprehensive mutasynthetic studies with three microbial strains (Actinosynnema pretiosum, Streptomyces hygroscopicus and Amycolatopsis mediterranei) blocked in the biosynthesis of aminohydroxybezoic acid (AHBA).

  • Publications
    • Franke, J., Eichner, S., Zeilinger, C., & Kirschning, A. (2013). Targeting heat-shock-protein 90 (Hsp90) by natural products: Geldanamycin, a show case in cancer therapy. Natural Product Reports, 30(10), 1299-1323.
    • Kirschning, A., & Hahn, F. (2012). Merging chemical synthesis and biosynthesis: A new chapter in the total synthesis of natural products and natural product libraries. Angewandte Chemie , 51(17), 4012-4022.,

    • Taft, F., Eichner, S., Knobloch, T., Harmrolfs, K., Hermane, J., & Kirschning, A. (2012). Ansamitocin libraries by combining mutasynthesis with chemical synthesis; A new version of total synthesis. Synlett, 23(10), 1416-1426. [ST-2011-A0246-A].
    • Kirschning, A., Harmrolfs, K., & Knobloch, T. (2008). The chemistry and biology of the maytansinoid antitumor agents. Comptes Rendus Chimie, 11(11-12), 1523-1543.
    • Kirschning, A., Taft, F., & Knobloch, T. (2007). Total synthesis approaches to natural product derivatives based on the combination of chemical synthesis and metabolic engineering. Organic and Biomolecular Chemistry, 5(20), 3245-3259.

Promiscuity of terpene cyclases

Terpenes are the most diverse class of secondary metabolites. They are generated from a linear precursor - in the case of sesquiterpenes this is farnesyl pyrophosphate (FPP) - by means of a cascade reaction. We demonstrated that sesquiterpene cyclases like presilphiperfolan-8-β-ol synthase (Bot2) show good substrate flexibility which allow to create new heteroatom-modified tricyclic sesquiterpenoids as shown for Bot2. For some new terpenoids GC-O analysis revealed an ethereal, peppery and camphor-like olfactoric scent.

  • Publications
    • Oberhauser, C., Harms, V., Seidel, K., Schröder, B., Ekramzadeh, K., Beutel, S., Winkler, S., Lauterbach, L., Dickschat, J. S., & Kirschning, A. (2018). Exploiting the Synthetic Potential of Sesquiterpene Cyclases for Generating Unnatural Terpenoids. Angewandte Chemie , 57(36), 11802-11806.,

SynMeth: methodology

Chemistry of hypervalent halides

In the years 1998 and 1999 we reported on the preparation of a new class of electrophilic halonium reagents, which are obtained by iodine(III)-mediated oxidation of bromide and iodide. The resulting haloate(I)-complexes can be further diversified by ligand exchange. These reagents show a large synthetic versatility.

Oxidative decarbonylation of aldehydes

The stereocontrolled palladium catalyzed umpolung allylation utilizes diboranes to yield intermediate allylboranes that directly react with aldehydes. Stereocontrol is best achieved when chiral aldehydes are employed.

  • Publications
    • Kipke, A., Schöning, K. U., Yusubov, M., & Kirschning, A. (2017). TEMPO-Mediated Oxidative Deformylation of Aldehydes: Applications in the Synthesis of Polyketide Fragments. European Journal of Organic Chemistry, 2017(46), 6906-6913.

Asymmetric formylation of aldehydes

Our concept of the asymmetric formylation of aldehydes is based on dissecting the C-C bond forming process and the establishment of the newly formed stereogenic center. This is achieved by Horner-Wittig olefination of the aldehyde followed by Sharpless asymmetric dihydroxylation of the intermediate O,O-ketene acetal.

Flow: synthetic technology

Flow chemistry

Our research programme on flow chemistry started in 1999 and led to a key publication in 2001 and an early key review in 2003. We cover the development of new, enabling technologies, immbolized (bio)catalysts, and multistep flow synthesis under continuous flow conditions. In 2008 we merged flow chemistry with inductive heating, an enabling technology suited to heat steel reactors or fixed-bed reactor materials based on copper or superparamagnetic nanoparticles (SPION). In combination with water as solvent this high temperature flow technology was exploited to carry out multistep syntheses of important drugs such as iloperidone.

Enabling technologies: inductive heating and flow

Inductive heating and mesofluidic reactors are a perfect match of two enabling technologies. Ferromagnetic materials (e.g. steel beads, copper metal) or superparamagnetic nanoparticles heat up in an oscillating electromagnetic field with medium (MF: 15-25 KHz) or high frequency (HF: 780-850 KHz) using appropriate inductors and coils.

  • Publications
    • Kirschning, A., Kupracz, L., & Hartwig, J. (2012). New synthetic opportunities in miniaturized flow reactors with inductive heating. Chemistry Letters, 41(6), 562-570.

TotalSyn: Totalsynthesis

Our total synthesis programme is embedded in a strategic partnership with the Helmholtz Center of Infection Deseases (Braunschweig/Saarbrücken). Here, our activities include the structure elucidation of new biologically highly potent secondary metabolites, their total and semisynthesis followed by their biological and biomedical profiling. Many of these natural products show either antiproliferative or antibacterial activities.

  • Carolacton

    Carolacton was isolated from Sorangium cellulosum and shows biofilm growth inhibition 0.005 µg/mL. Planktonic cultures are insensitive to Carolacton.

    • Donner, J., Reck, M., Bunk, B., Jarek, M., App, C. B., Meier-Kolthoff, J. P., Overmann, J., Müller, R., Kirschning, A., & Wagner-Döbler, I. (2017). The biofilm inhibitor carolacton enters Gram-negative cells: Studies using a Tol-Cdeficient strain of Escherichia coli. mSphere, 2(5), [e00375-17]. 10.1128/mSphereDirect.00375-17
    • Donner, J., Reck, M., Bergmann, S., Kirschning, A., Müller, R., & Wagner-Döbler, I. (2016). The biofilm inhibitor Carolacton inhibits planktonic growth of virulent pneumococci via a conserved target. Scientific Reports, 6, [29677].
    • Stumpp, N., Premnath, P., Schmidt, T., Ammermann, J., Dräger, G., Reck, M., Jansen, R., Stiesch, M., Wagner-Döbler, I., & Kirschning, A. (2015). Synthesis of new carolacton derivatives and their activity against biofilms of oral bacteria. Organic and Biomolecular Chemistry, 13(20), 5765-5774.
    • Schmidt, T., & Kirschning, A. (2011). Total synthesis of carolacton, a highly potent biofilm inhibitor. Angewandte Chemie , 51(4), 1063-1066.,
    • Jansen, R., Irschik, H., Huch, V., Schummer, D., Steinmetz, H., Bock, M., Schmidt, T., Kirschning, A., & Müller, R. (2010). Carolacton - A macrolide ketocarbonic acid that reduces biofilm formation by the caries- and endocarditis-associated bacterium Streptococcus mutans. European Journal of Organic Chemistry, (7), 1284-1289.
  • Elansolid A1 and A2

    Elansolid A1 and A2 were isolated from gliding bacterium Chitinophaga. They show antibacterial activity (including Staphylococcus aureus and Micrococcus luteus).

    • Wang, L., & Kirschning, A. (2017). Total synthesis of elansolids B1 and B2. Beilstein Journal of Organic Chemistry, 13, 1280-1287.
    • Wang, L., Candito, D., Dräger, G., Herrmann, J., Müller, R., & Kirschning, A. (2017). Harnessing a p-Quinone Methide Intermediate in the Biomimetic Total Synthesis of the Highly Active Antibiotic 20-Deoxy-Elansolid B1. Chemistry - A European Journal, 23(22), 5291-5298.
    • Weber, A., Dehn, R., Schläger, N., Dieter, B., & Kirschning, A. (2014). Total synthesis of the antibiotic Elansolid B1. Organic Letters, 16(2), 568-571.
    • Steinmetz, H., Zander, W., Shushni, M. A. M., Jansen, R., Gerth, K., Dehn, R., Dräger, G., Kirschning, A., & Müller, R. (2012). Precursor-Directed Syntheses and Biological Evaluation of New Elansolid Derivatives. ChemBioChem, 13(12), 1813-1817.
    • Dehn, R., Katsuyama, Y., Weber, A., Gerth, K., Jansen, R., Steinmetz, H., Höfle, G., Müller, R., & Kirschning, A. (2011). Molecular basis of elansolid biosynthesis: Evidence for an unprecedented quinone methide initiated intramolecular diels-alder cycloaddition/ macrolactonization. Angewandte Chemie , 50(17), 3882-3887.,
    • Jansen, R., Gerth, K., Steinmetz, H., Reinecke, S., Kessler, W., Kirschning, A., & Müller, R. (2011). Elansolid A3, a unique p-quinone methide antibiotic from Chitinophaga sancti. Chemistry - A European Journal, 17(28), 7739-7744.
    • Steinmetz, H., Gerth, K., Jansen, R., Dehn, R., Reinecke, S., Kirschning, A., & Müller, R. (2011). Elansolid A, a Unique Macrolide Antibiotic from Chitinophaga sancti Isolated as Two Stable Atropisomers. Angewandte Chemie , 50(2), 532-536.,
  • Cystobactamid 861-2

    Cystobactamid 861-2 was isolated from Cystobacter sp. and possesses strong antibacterial activity. This compound is a inhibitor of bacterial topoisomerase.

    • Planke, T., Moreno, M., Hüttel, S., Fohrer, J., Gille, F., Norris, M. D., Siebke, M., Wang, L., Müller, R., & Kirschning, A. (2019). Cystobactamids 920-1 and 920-2: Assignment of the Constitution and Relative Configuration by Total Synthesis. Organic Letters, 21(5), 1359-1363.
    • Hüttel, S., Testolin, G., Herrmann, J., Planke, T., Gille, F., Moreno, M., Stadler, M., Brönstrup, M., Kirschning, A., & Müller, R. (2017). Discovery and Total Synthesis of Natural Cystobactamid Derivatives with Superior Activity against Gram-Negative Pathogens. Angewandte Chemie , 56(41), 12760-12764.,


  • Thuggacin A

    Thuggacin A was isolated from myxobacterium Sorangium cellulosum and shows strong antibiotic activity (including Mycobacterium tuberculosis). It targets the bacterial respiratory chain.

Targeted drug delivery

In our group a concept that combines drug delivery, targeting and release was developed that relies on nontoxic superparamagnetic ironoxide nanoparticles (SPION) – maytansinoid conjugates that bear a heat sensitive linker. Release of the toxic maytansinoid is achieved by inductive heating of the SPION which activates the thermosensitive linker. Proof of concept was demonstrated for cancer cell lines (in vitro) and for solid tumours (in vitro). For successful drug delivery and targeting  we exploit the fact that in our case liver-specific macrophages are able to take-up nanoparticles including our SPION – maytansinoid conjugates and these macrophage transport systems undergo apoptosis followed by liberation of the toxin in an oscillating electromagnetic field.

  • Publications
    • Norris, M. D., Seidel, K., & Kirschning, A. (2019). Externally Induced Drug Release Systems with Magnetic Nanoparticle Carriers: An Emerging Field in Nanomedicine. Advanced Therapeutics, 2(1), [1800092].
    • Ullah, S., Seidel, K., Türkkan, S., Warwas, D. P., Dubich, T., Rohde, M., Hauser, H., Behrens, P., Kirschning, A., Köster, M., & Wirth, D. (2019). Macrophage entrapped silica coated superparamagnetic iron oxide particles for controlled drug release in a 3D cancer model. Journal of controlled release, 294, 327-336.
    • Seidel, K., Balakrishnan, A., Alexiou, C., Janko, C., Komoll, R. M., Wang, L., Kirschning, A., & Ott, M. (2017). Synthesis of Magnetic-Nanoparticle/Ansamitocin Conjugates: Inductive Heating Leads to Decreased Cell Proliferation In Vitro and Attenuation Of Tumour Growth In Vivo. Chemistry - A European Journal, 23(50), 12326-12337.
    • Wang, L. L., Balakrishnan, A., Bigall, N. C., Candito, D., Miethe, J. F., Seidel, K., Xie, Y., Ott, M., & Kirschning, A. (2017). A Bio-Chemosynthetic Approach to Superparamagnetic Iron Oxide–Ansamitocin Conjugates for Use in Magnetic Drug Targeting. Chemistry - a European journal, 23(10), 2265-2270.


Prof. Dr. rer. nat. Andreas Kirschning
Schneiderberg 1B
30167 Hannover
Prof. Dr. rer. nat. Andreas Kirschning
Schneiderberg 1B
30167 Hannover