Gram Scale Synthesis of Membrane-Active Antibacterial 4-Quinolone Lead Compound

Gorakhnath Jachak; Moyosore O Orimoloye; Courtney C. Aldrich

doi:10.1021/acs.joc.3c00239

Gram Scale Synthesis of Membrane-Active Antibacterial 4-Quinolone Lead Compound

Gorakhnath Jachak, Moyosore O Orimoloye, Courtney C. Aldrich

Medicinal Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

An improved method for the synthesis of a new quinolone class of antibiotics, which are exceptionally potent against gram-positive bacteria, has been developed and the structure confirmed by single-crystal X-ray analysis. In the course of synthesis, using either Chan-Lam coupling or Buchwald-Hartwig amination, we have shown that the careful choice of protecting group at the C4 position of the quinoline is required for selective amination at the C5 position and subsequent deprotection to avoid the formation of a novel pyrido[4,3,2-de]quinazoline tetracycle.

Original language	English (US)
Journal	Journal of Organic Chemistry
DOIs	https://doi.org/10.1021/acs.joc.3c00239
State	Accepted/In press - 2023

Bibliographical note

Funding Information:
This work was supported by RO1 AI146116 and R21 AI130540. We would like to thank Dr. Victor G. Young, Jr. from the Department of Chemistry, University of Minnesota for X-ray crystallographic analysis.

Publisher Copyright:
© 2023 American Chemical Society

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abstract = "An improved method for the synthesis of a new quinolone class of antibiotics, which are exceptionally potent against gram-positive bacteria, has been developed and the structure confirmed by single-crystal X-ray analysis. In the course of synthesis, using either Chan-Lam coupling or Buchwald-Hartwig amination, we have shown that the careful choice of protecting group at the C4 position of the quinoline is required for selective amination at the C5 position and subsequent deprotection to avoid the formation of a novel pyrido[4,3,2-de]quinazoline tetracycle.",

author = "Gorakhnath Jachak and Orimoloye, {Moyosore O} and Aldrich, {Courtney C.}",

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Gram Scale Synthesis of Membrane-Active Antibacterial 4-Quinolone Lead Compound

Abstract

Bibliographical note

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