108351-50-4Relevant articles and documents
Concise Chemoenzymatic Total Synthesis and Identification of Cellular Targets of Cepafungin I
Amatuni, Alexander,Shuster, Anton,Adibekian, Alexander,Renata, Hans
, p. 1318 - 18,1326 (2020)
Amatuni et al. established a concise chemoenzymatic synthesis of cepafungin I. The route enabled access to a chemoproteomic probe, revealing high selectivity for proteasome subunits β5/2. Potent inhibition was associated with the macrocyclic hydroxyl group and lipid tail. Cepafungin I exhibited similar mode of action with the clinical drug bortezomib. The natural product cepafungin I was recently reported to be one of the most potent covalent inhibitors of the 20S proteasome core particle through a series of in vitro activity assays. Here, we report a short chemoenzymatic total synthesis of cepafungin I featuring the use of a regioselective enzymatic oxidation to prepare a key hydroxylated amino acid building block in a scalable fashion. The strategy developed herein enabled access to a chemoproteomic probe, which in turn revealed the exceptional selectivity and potency of cepafungin I toward the β2 and β5 subunits of the proteasome. Further structure-activity relationship studies suggest the key role of the hydroxyl group in the macrocycle and the identity of the lipid tail in modulating the potency of this natural product family. This study lays the groundwork for further medicinal chemistry exploration to fully realize the anticancer potential of cepafungin I.
The Synthesis of Glidobactin A
Schmidt, Ulrich,Kleefeldt, Andreas,Mangold, Rainer
, p. 1687 - 1689 (2007/10/02)
Glidobactin A, a member of the antibiotic families glidobactins and cepafungins, which was previously isolated from culture filtrates of the Gram-negative bacterium Polyanginum brachysporum sp. nov., is synthesized.
