Researchers in the Del Valle Group, published in Organic Letters, report the total synthesis and configurational assignment of pargamicin A, a highly oxidized nonribosomal peptide that potently inhibits the growth of drug-resistant bacteria. Their synthetic approach relies on late-stage piperazine ring formation and careful selection of condensation reagents to assemble the densely substituted hexapeptide backbone.

This work enables the synthesis of pargamicin congeners for the development of structure–activity relationships and informs strategies for accessing other sterically congested piperazic acid-containing natural products.

Title:
Total Synthesis of Pargamicin A
Authors:
Yassin M. Elbatrawi, Taylor Gerrein, Avraz Anwar, Kamlesh M. Makwana, David Degen, Richard H. Ebright, and Juan R. Del Valle
Citation:
Org. Lett. 2022, 24, 50, 9285–9289
URL:
https://doi.org/10.1021/acs.orglett.2c03861

The Del Valle Group