Natural product synthesis and derivatisation

Many natural products are only produced in minor amounts and a full structural characterization is nearly impossible. In addition, many pharmaceutically interesting compounds are too toxic and need derivatisation to improve their pharmacological properties.

Therefore, we are establishing synthetic strategies towards sphingoid-type natural products and functionalized lipids, which represent important signaling molecules in our ecological mdoel systems. 

Synthesis of new NRPS-derived natural products

Based on a comparative genome analysis, we were able to isolate a new natural product - barnesin A. Further bioactivity studies showed that barnesin A is a cysteine ​​protease inhibitor with nanomolar activity. The total synthesis enabled further structural activity studies.

For more details, see Maja's article in ACS ChemBio!

Staff

Daniel Leichnitz
Luka Raguž
David Roman
Maria Sauer

Publications

Grosse M, Günther K, Jordan PM, Roman D, Werz O, Beemelmanns C (2022) Synthesis of functionalized δ-hydroxy-β-keto esters and evaluation of their anti-inflammatory properties. Chembiochem 23(9), e202200073.
Sauer M, Beemelmanns C (2022) Application of pyrrolo-protected amino aldehydes in the stereoselective synthesis of anti 1,2-amino alcohols. ChemCom 58(64), 8990-8993.
Raguž L, Peng CC, Kaiser M, Görls H, Beemelmanns C* (2021) A modular approach to the antifungal Sphingofungin family: Concise total synthesis of Sphingofungin A and C. Angew Chem Int Ed 61(5), e202112616.
Roman D, Sauer M, Beemelmanns C (2021) Applications of the Horner-Wadsworth-Emmons olefination in modern natural product synthesis. Synthesis 53(16), 2713-2739. (Review)
Hubert P, Seibel E, Beemelmanns C, Campagne JM, de Figueiredo RM (2020) Stereoselective construction of (E,Z)-1,3-dienes and its application in natural product synthesis. Adv Synth Catal 362(24), 5532-5575. (Review)
Beemelmanns C, Nitsch D, Bentz C, Reissig HU (2019) Stereoselective cascade cyclizations with samarium diiodide to tetracyclic indolines - precursors of fluorostrychnines and brucine. Chemistry 25(37), 8780-8789.
Leichnitz D, Pflanze S, Beemelmanns C (2019) Stereoselective synthesis of unnatural (2S,3S)-6-hydroxy-4-sphingenine-containing sphingolipids. Org Biomol Chem 17(29), 6964-6969.
Raguz L, Beemelmanns C (2019) Ursprung und Funktionen der Sphingolipide. Nachrichten aus der Chemie 67(2), 66-70. (Review)
Rischer M, Raguz L, Guo H, Keiff F, Diekert G, Goris T, Beemelmanns C (2018) Biosynthesis, synthesis and activities of barnesin A, a NRPS-PKS hybrid produced by an anaerobic Epsilonproteobacterium. ACS Chem Biol 13(8), 1990-1995.
Leichnitz D, Raguž L, Beemelmanns C (2017) Total synthesis and functional analysis of microbial signalling molecules. Chem Soc Rev 46(20), 6330-6344. (Review)