Published In

Journal of Medicinal Chemistry

Document Type

Post-Print

Publication Date

6-10-2021

Subjects

Malaria -- Prevention -- Research

Abstract

Highly efficient and straightforward synthetic routes toward the first total synthesis of 2-(-hydroxybenzyl)-prodigiosins (-), isoheptylprodigiosin (), and geometric isomers of tambjamine MYP1 ((/)-) have been developed. The crucial steps involved in these synthetic routes are the construction of methoxy-bipyrrole-carboxaldehydes (MBCs) and a 20-membered macrocyclic core and a regioselective demethylation of MBC analogues. These new synthetic routes enabled us to generate several natural prodiginines - in larger quantity. All of the synthesized natural products exhibited potent asexual blood-stage antiplasmodial activity at low nanomolar concentrations against a panel of parasites, with a great therapeutic index. Notably, prodiginines and - provided curative in vivo efficacy against erythrocytic at 25 mg/kg × 4 days via oral route in a murine model. No overt clinical toxicity or behavioral change was observed in any mice treated with prodiginines and tambjamines.

Rights

Copyright © 2021 American Chemical Society

Description

This is the author’s version of a work that was accepted for publication in the Journal of Medicinal Chemistry. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Medicinal Chemistry.

Version of record: https://doi.org/10.1021/acs.jmedchem.1c00748

DOI

10.1021/acs.jmedchem.1c00748

Persistent Identifier

https://archives.pdx.edu/ds/psu/35953

Supporting Information-Final.pdf (3353 kB)
Supporting Information

Molecular formula strings (1).csv (3 kB)
Molecular Formula Strings

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