Conformation-guided analogue design identifies potential antimalarial compounds through inhibition of mitochondrial respiration

文献信息

发布日期 2018-07-11
DOI 10.1039/C8OB01257A
影响因子 3.876
作者

Erik M. Larsen, Chia-Fu Chang, Tomoyo Sakata-Kato, Joseph W. Arico, Vince M. Lombardo, Dyann F. Wirth, Richard E. Taylor


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摘要

The synthesis of a 2-methyl-substituted analogue of the natural product, neopeltolide, is reported in an effort to analyze the importance of molecular conformation and ligand–target interactions in relation to biological activity. The methyl substitution was incorporated via highly diastereoselective ester enolate alkylation of a late-stage intermediate. Coupling of the oxazole sidechain provided 2-methyl-neopeltolide and synthetic neopeltolide via total synthesis. The substitution was shown to maintain the conformational preferences of its biologically active parent compound through computer modeling and NMR studies. Both compounds were shown to be potential antimalarial compounds through the inhibition of mitochondrial respiration in P. falciparum parasites.

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来源期刊

Organic & Biomolecular Chemistry

Organic & Biomolecular Chemistry
CiteScore: 3.4
自引率: 10.3%
年发文量: 1041

Organic & Biomolecular Chemistry (OBC) publishes original and high impact research and reviews in organic chemistry. We welcome research that shows new or significantly improved protocols or methodologies in total synthesis, synthetic methodology or physical and theoretical organic chemistry as well as research that shows a significant advance in the organic chemistry or molecular design aspects of chemical biology, catalysis, supramolecular and macromolecular chemistry, theoretical chemistry, mechanism-oriented physical organic chemistry, medicinal chemistry or natural products. Articles published in the journal should report new work which makes a highly-significant impact in the field. Routine and incremental work is generally not suitable for publication in the journal. More details about key areas of our scope are below. In all cases authors should include in their article clear rationale for why their research has been carried out.

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