Abstract
Natural products (NPs) are an important inspirational source for developing drugs and chemical probes. In 1999, the group of Ōmura reported the constitutional elucidation of zelkovamycin. Although largely unrecognized so far, this NP displays structural similarities as well as differences to the argyrin NP family, a class of peptidic NPs with promising anticancer activities and diverse mode‐of‐action at the molecular level. By a combination of structure elucidation experiments, the first total synthesis of zelkovamycin and bioassays, the zelkovamycin configuration was determined and its previously proposed molecular structure was revised. The full structure assignment proves zelkovamycin as an additional member of the argyrins with however unique OXPHOS inhibitory properties. Zelkovamycin may therefore not only serve as a new starting point for chemical inhibitors of the OXPHOS system, but also guide customized argyrin NP isolation and biosynthesis studies.
Highlights
Natural products (NPs) are an important inspirational source for developing drugs and chemical probes
In 1999, the group of Omura reported the isolation of the NP zelkovamycin as a moderately potent antibacterial cycloheptapeptide from a fermentation broth of Streptomyces sp
Despite the striking structural similarities between zelkovamycin and the argyrins, there are distinct differences: Most obviously, argyrins typically feature a 4-methoxy tryptophan ((4MeO)Trp) or an unsubstituted Trp, but never a (7-MeO)Trp residue, as reported for zelkovamycin.[4a–c] the position of the (4-MeO)Trp residue in the argyrins is occupied by the unusual (2-Me)DThr moiety in zelkovamycin, while the
Summary
Natural products (NPs) are an important inspirational source for developing drugs and chemical probes.
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