Total Synthesis of Pargamicin A

15 November 2022, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

We report the total synthesis and configurational assignment of pargamicin A, a highly oxidized non-ribosomal peptide that potently inhibits the growth of drug-resistant bacteria. Our 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 to access other sterically congested piperazic acid-containing natural products.

Keywords

natural products
piperazic acid
electrophilic amination
antibiotic
non-ribosomal peptide

Supplementary materials

Title
Description
Actions
Title
Supporting Information
Description
Detailed experimental procedures, characterization data for novel compounds, copies of RP-HPLC, HRMS, NMR spectra (PDF), and biological assay data.
Actions

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.