Latest publications 

  S. Ullah, K. Seidel, S. Türkkan, D.P. Warwas, T. Dubich, M. Rohde, H. Hauser, P Behrens, A. Kirschning, M. Köster, D. Wirth:

Macrophage entrapped silica coated superparamagnetic iron oxide particles for controlled drug release in a 3D cancer model.

Journal of Controlled Release 2019, 294, 327–336.



Targeted delivery of drugs is a major challenge in treatment of diverse diseases. Systemically administered drugs demand high doses and are accompanied by poor selectivity and side effects on non-target cells. Here, we introduce a new principle for targeted drug delivery. It is based on macrophages as transporters for nanoparticle-coupled drugs as well as controlled release of drugs by hyperthermia mediated disruption of the cargo cells and simultaneous deliberation of nanoparticle-linked drugs. Hyperthermia is induced by an alternating electromagnetic field (AMF) that induces heat from silica-coated superparamagnetic iron oxide nanoparticles (SPIONs). We show proof-of-principle of controlled release by the simultaneous disruption of the cargo cells and the controlled, AMF induced release of a toxin, which was covalently linked to silica-coated SPIONs via a thermo-sensitive linker. Cells that had not been loaded with SPIONs remain unaffected. Moreover, in a 3D co-culture model we demonstrate specific killing of associated tumour cells when employing a ratio as low as 1:40 (SPION-loaded macrophage: tumour cells). Overall, our results demonstrate that AMF induced drug release from macrophage-entrapped nanoparticles is tightly controlled and may be an attractive novel strategy for targeted drug release

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 C. Oberhauser, V. Harms, K. Seidel, B. Schröder, K. Ekramzadeh, S. Beutel, S. Winkler, L. Lauterbach,  J. S.Dickschat, A. Kirschning:

Exploiting the synthetic potential of sesquiterpene cyclases for generating unnatural terpenoids.

Chem. Eur. J. 2018, 648 –656.



Flexibility for new scents: Eight sesquiterpene cyclases from fungal, bacterial and plant sources were tested to transform 6 heteroatom functionalized farnesylpyrophosphate derivatives. Bot2 yielded a novel tricyclic product in 36 % yield. The olfactoric analysis revealed an ethereal, peppery and camphoric scent. 

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M. Wolling, A. Kirschning :

Synthesis of the aglycon of the antibiotic disciformycin

Chem. Eur. J. 2018, 648 –656.



Challenging alkenes:  The synthesis of the aglycon of disciformycin, a new secondary metabolite from Pyxidicoccus fallax, with high antibacterial potency is reported. The stereocontrolled installation of the olefinic double bonds at C2-C3/C3-C4 and C12-C13, respectively, as well the orthogonal differentiation of the oxy functionalities unexpectedly were found to be key challenges of the project. 


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A. Kirschning, N. Dibbert, G. Dräger :

Chemical functionalization of polysaccharides – towards biocompatible hydrogels for biomedical applications

Chem. Eur. J. 2018, 24, 1231 –1240.


nick-paper-2018.jpgHydrogels have emerged as a highly interdisciplinary topic as they play a significant role for a vast number of applications. Few of them include as materials for contact lenses, wound dressing or as filler material in soft-tissue augmentation. More recently, polysaccharides have received attention, particularly in the fields of regenerative medicine and tissue engineering, as ideal candidate materials for artificial extracellular matrices (ECM).The polysaccharidesof choice are dextran,alginate, chitosan, hyaluronic acid and pullulan and in order to obtain suitable hydrogels from these polysaccharides,controlled chemical functionalization is of critical importance.This short review summarizes recent developments in the chemical derivatization of polysaccharides to pave the way for crosslinking and to decorate individual polysaccharide chains with bioactive ligands. The report covers convergent and divergent protocols for crosslinking,as well strategies for bisfunctionalization of polysaccharides. Additionally, information on biological properties and biomedical applications are covered.

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H. Sommer, M. Braun, B. Schröder, A. Kirschning :

4-Ethoxy-1,1,1-trifluoro-3-buten-2-one (ETFBO), a versatile precursor for trifluoromethyl substituted hetarenes – a short synthesis of Celebrex® (Celecoxib)

Synlett 2018, 29, 121-125.


benny-paper.jpg4-Ethoxy-1,1,1-trifluoro-3-buten-2-one (ETFBO) serves as a trifluoromethyl containing building block for the preparation of trifluoromethyl-substituted thiophenes, furans, pyrrols and piperazines. Key steps are an addition-elimination reaction to ETFBO followed by the thiazolium catalysed Stetter reaction. The scope of this chemistry was demonstrated in a new synthetic approach towards the COX-2 selective,non-steroidal anti-inflammatory drug Celebrex® (celecoxib).

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M. S. Yusubov, P. S. Postnikov, R. Y. Yusubova,A. Yoshimura, G. Jürjens, A. Kirschning, V. V. Zhdankine:

2-Iodoxybenzoic Acid Tosylates: the Alternative to Dess–Martin Periodinane
Oxidizing Reagents

 Adv. Synth. Catal. 2017, 359, 3207-3216


untitled.jpgTwo powerful hypervalent iodine(V) oxidants, DMP-OTs
(1-tosyloxy-1,1-diacetoxy-1H-1l5-benzo[d][1,2]iodoxol-3-one) and IBX-OTs (1-tosyloxy-1-oxo-1H-1l5-benzo[d][1,2]iodoxol-3-one) show high reactivity in the oxidation of structurally complex primary and secondary alcohols, which are highly functionalized polyketide or terpene fragments or steroids. The yields of the corresponding carbonyl compounds are even higher for the protocol that uses pyridine as additive. The oxidations proceed very rapidly at room temperature leaving the protective groups and p-systems intact and affording the corresponding carbonyl compounds in good to excellent yields. Moreover, IBX-OTs is an efficient reagent for the oxidative dehydrogenation
of steroidal alcohols to the corresponding enones.

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 S. Hüttel, G. Testolin, J. Herrmann,T. Planke, F. Gille, M. Moreno, M. Stadler, M. Brönstrup, A. Kirschning, R. Müller:

Discovery and total synthesis of natural cystobactamid derivatives with superior activity against Gram-negative pathogens

Angew. Chem. Int. Ed. 2017, 56, 12760-12764


From nature’s toolbox: A concise study with myxobacterial producer strains yielded novel cystobactamid derivatives that display superior activity on Gram-negative pathogens including clinical isolates. The first total synthesis of the most promising derivative was accomplished and will serve as a starting point for the further optimization of these gyrase inhibitors
and their development as antibacterial drugs.

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 L.-L. Wang, D. Candito, G. Dräger, A. Kirschning:

Synthetic Studies Probing Elansolid Biosynthesis: A para-Quinone Methide Triggered Intramolecular Diels-Alder Reaction

Eur. J. Org. Chem. 2017, 37, 5582-5591.


graphabstr_1.jpgThe tetrahydroindane unit of the elansolids A1/A2 and B1-B3 is supposed to be formed by an intramolecular Diels-Alder cycloaddition (IMDA). To study the biosynthetic proposal,the influence of an oxy-functionality at C-20, the regiochemistry of the allylic alcohol precursor as well as the nature of the phenol group were investigated. The oxy-functionality at C-20 has a  profound effect on the outcome of this reaction leading to a Prins-type reaction cascade initiated by a p-quinone methide intermediate, that leads to an unexpected cycloadduct. The corresponding 20-deoxy precursor, as suggested for the naturally occurring IMDA precursor smoothly yields the desired IMDA product as mixture of two endo products. These results support the hypothesis that nature likely utilizes an intramolecular Diels-Alder cycloaddition to generate the bicyclic core of the elansolids starting from of 20-deoxygenated precursor.

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K. Seidel, A. Balakrishnan, C. Alexiou , C. Janko, R-M Komoll, L.-L. Wang, A. Kirschning, M Ott:

Synthesis of Magnetic-Nanoparticle/Ansamitocin Conjugates- Inductive Heating Leads to Decreased Cell Proliferation In Vitro and Attenuation of Tumour Growth In Vivo

Chem. Eur. J. 2017, 23, 12326-12337.


mouse-picture2-2.jpgIn vivo drug release: The preparation of conjugates composed of a modified toxic ansamitocin, obtained through precursor-directed biosynthesis and semisynthesis, a thermeosensitive linker and super-paramagnetic, nanostructured particles provide an antitumour concept to combine hyperthermia with chemotherapy in anticancer research. In vitro evaluation and in In vivo xenograft experiments demonstrate the proof of concept.

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L. L. Wang,  A. Kirschning:

Total synthesis of elansolids B1 and B2

Beilstein J. Org. Chem. 2017, 13, 1280-1287

graphabstr.jpgThe elansolids A1-A3, B1, and B2 are secondary metabolites formed by the gliding bacterium Chitinophaga sancti. They show antibacterial activity against Gram-positive bacteria. A second generationtotal synthesis of the antibiotic elansolid B1 (2) and the
first synthesis of elansolid B2 (3) are reported. In contrast to previous work, the (Z,E,Z)-triene at C10-C15 was assembled by using an optimized C-C cross-coupling sequence with a Suzuki cross-coupling reaction as key step.

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L. L. Wang, D. Candito,  G. Dräger, J. Herrmann, R. Müller, A. Kirschning:

Harnessing a p-Quinone Methide Intermediate in the Biomimetic Total Synthesis of the Highly Active Antibiotic 20-Deoxy-Elansolid B1

Chem. Eur. J. 2017, 23, 5291-5298.

350-graphabstr.jpgThe polyketide, 20-deoxy elansolid B1, was prepared by a convergent strategy that relied on a putative biomimetic intramolecular Diels–Alder cycloaddition (IMDA) via a vinylic p-quinone methide intermediate to furnish the key tetrahydroindane unit. The (Z,E,Z)-configured triene unit was constructed by Pd-catalyzed Suzuki–Miyaura and Stille crosscoupling reactions without isomerization of any of the olefinic double bonds. Formation of a p-methide quinone intermediate under basic conditions and subsequent Michael addition by water to this intermediate proceeded with high facial selectivity which terminated this total synthesis. Remarkably, the new elansolid derivative 2c shows very good inhibitory effect against Bacillus subtilis and Staphylococcus aureus (including MRSA) similarly to the best elansolid derivatives reported so far. Consequently, the hydroxyl group at C20 is not essential for antibacterial activity.

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L.-L. Wang, A. Balakrishnan, N.-C. Bigall, D. Candito, J.F. Miethe, Y. Xie, K. Seidel, M. Ott, A. Kirschning:

A bio-chemosynthetic approach to superparamagnetic iron oxide - ansamitocin conjugates for use in magnetic drug targeting (MDT)

Chem. Eur. J. 2017, 23, 2265–2270.

350-2.jpgHot and toxic! The combination of muta- and semisynthesis yields a modified toxic ansamitocin, which was loaded to functionalized super-paramagnetic, nanostructured particles. The toxin (IC50 in the lower nanomolar range) was released in an external electromagnetic field through inductive heating. The conjugate concept allows the combination of hyperthermia with chemotherapy in anticancer research.

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S. Ceylan, H. C.-H. Law, A. Kirschning, P. H. Toy:

Organocatalytic Alkyne Isomerizations under Flow Conditions Using Heterogeneous Bifunctional Polystyrene Bearing Phosphine and Phenol Groups

Synthesis 2017, 49, 145-150.

flow350.jpgA heterogeneous bifunctional polymer bearing phosphine and phenol groups was developed to catalyze the isomerization of electronically activated alkynes. This organocatalytic process provided the corresponding (E,E)-dienes and was shown to work under both batch and flow conditions. 

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R. Sharma, S. Mohammadi-Ostad-Kalayeh, F. Stahl, C. Zeilinger, G. Dräger, A. Kirschning, P.C. Ravikumar:

Two new labdane diterpenoids and one new β-lactam from the aerial parts of Roylea cinerea

Phytochem. Lett. 2017, 19, 101-107.

roylea200.jpgTwo new labdane diterpenoids cinereanoid C (1), cinereanoid D (2), a new β-lactam, cinerealactam E (3) as well as six known flavonoid glycosides (4–9) were isolated from the aerial parts of Roylea cinerea (Lamiaceae). The structures of (1–9) were all determined by MS, IR and NMR spectroscopy. The structure of cinereanoid D (2) was further proven by single crystal X-ray diffraction. Six known flavonoid glycosides (4–9) were also isolated for the first time from this plant. 2, 5, 6 and 7 were found to significantly inhibit the ATP binding of a tumour growth-promoting heat shock protein, Hsp90. 

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N. Dibbert, A. Krause, J.-C. Rios-Camacho, I. Gruh, A. Kirschning, G. Dräger:

A Synthetic Toolbox for the In Situ Formation of Functionalized Homo- and Heteropolysaccharide- Based Hydrogel Libraries

Chem. Eur. J. 2016, 52, 18777-18786.

toolbox350.jpgA synthetic toolbox for the introduction of aldehydo and hydrazido groups into the polysaccharides hyaluronic acid, alginate, dextran, pullulan, glycogen, and carboxymethyl cellulose and their use for hydrogel formation is reported. Upon mixing differently functionalized polysaccharides derived from the same natural precursor, hydrazone cross-linking takes place, which results in formation of a hydrogel composed of one type of polysaccharide backbone. Likewise, hydrogels based on two different polysaccharide strands can be formed after mixing the corresponding aldehydo- and hydrazido-modified polysaccharides. A second line of these studies paves the way to introduce a biomedically relevant ligand, namely, the adhesion factor cyclic RGD pentapeptide, by using an orthogonal click reaction. This set of modified polysaccharides served to create a library of hydrogels that differ in the combination of polysaccharide strands and the degree of cross-linking. The different hydrogels were evaluated with respect to their rheological properties, their ability to absorb water, and their cytotoxicity towards human fibroblast cell cultures. None of the hydrogels studied were cytotoxic, and, hence, they are in principal biocompatible for applications in tissue engineering. 

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T. Pfeffer, F. Sasse, C. F. Schmidt, S. Lakämpfer, A. Kirschning, T. Scholz:

The natural diterpene tonantzitlolone A and its synthetic enantiomer inhibit cell proliferation and kinesin-5 function

Eur. J. Med. Chem. 2016, 112, 164-170.

tonantzitolone-pfeffer350.jpgTonantzitlolone A, a diterpene isolated from the Mexican plant Stillingia sanguinolenta, shows cytostatic activity. Both the natural product tonantzitlolone A and its synthetic enantiomer induce monoastral spindle formation in cell experiments which indicates inhibitory activity on kinesin-5 mitotic motor molecules. These inhibitory effects on kinesin-5 could be verified in in vitro single-molecule motility assays, where both tonantzitlolones interfered with kinesin-5 binding to its cellular interaction partner microtubules in a concentration-dependent manner, yet with a larger effect of the synthetic enantiomer. In contrast to kinesin-5 inhibition, both tonantzitlolone A enantiomers did not affect conventional kinesin-1 function; hence tonantzitlolones are not unspecific kinesin inhibitors. The observed stronger inhibitory effect of the synthetic enantiomer demonstrates the possibility to enhance the overall moderate anti-proliferative effect of the lead compound tonantzitlolon A by chemical modification.


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