@article{6be089a7e7474de78989a3d0afa83337,
title = "New Scalable Synthetic Routes to ELQ-300, ELQ-316, and Other Antiparasitic Quinolones",
abstract = "The endochin-like quinolone (ELQ) compound class may yield effective, safe treatments for a range of important human and animal afflictions. However, to access the public health potential of this compound series, a synthetic route needed to be devised, which would lower costs and be amenable to large-scale production. In the new synthetic route described here, a substituted β-keto ester, formed by an Ullmann reaction and subsequent acylation, is reacted with an aniline via a Conrad-Limpach reaction to produce 3-substituted 4(1H)-quinolones such as ELQ-300 and ELQ-316. This synthetic route, the first described to be truly amenable to industrial-scale production, is relatively short (five reaction steps), does not require palladium, chromatographic separation, or protecting group chemistry, and may be performed without high vacuum distillation.",
keywords = "Conrad-Limpach reaction, ELQ-300, ELQ-316, Ullmann reaction, antimalarial, antiparasitic, practical synthesis, process development",
author = "Sovitj Pou and Dodean, {Rozalia A.} and Lisa Frueh and Liebman, {Katherine M.} and Gallagher, {Rory T.} and Haihong Jin and Jacobs, {Robert T.} and Aaron Nilsen and Stuart, {David R.} and Joseph Doggett and Riscoe, {Michael K.} and Winter, {Rolf W.}",
note = "Funding Information: This project was supported with funds from the United States Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development Program, with additional supplemental funding from VA Technology Transfer, Merit Review Grant award number i01 BX003312 (M.K.R.). M.K.R. is a recipient of a VA Research Career Scientist Award (14S-RCS001). Research reported in this publication was also supported by the US National Institutes of Health under award numbers R01AI100569 and R01AI141412 (M.K.R.) and by the US Department of Defense Peer Reviewed Medical Research Program (Log # PR181134) (M.K.R.). This work was also funded by the Career Development Award BX002440 and VA Merit Review Award BX004522 to J.S.D. from the US Department of Veterans Affairs Biomedical Laboratory Research and Development. The National Science Foundation provided instrument funding for the BioAnalytical Mass Spectrometry Facility at Portland State University (NSF, MRI 1828573). The Medicines for Malaria Venture supported the discovery of ELQ-300 , and the authors would like to acknowledge their continued involvement in this project. The authors would also like to acknowledge the contributions of the OHSU Medicinal Chemistry Core. Publisher Copyright: {\textcopyright} 2021 American Chemical Society.",
year = "2021",
month = aug,
day = "20",
doi = "10.1021/acs.oprd.1c00099",
language = "English (US)",
volume = "25",
pages = "1841--1852",
journal = "Organic Process Research and Development",
issn = "1083-6160",
publisher = "American Chemical Society",
number = "8",
}