Design, organocatalytic synthesis, and bioactivity evaluation of enantiopure fluorinated LpxC inhibitors

Melanie Rodríguez-Alvarado; Riccardo Russo; Nancy D. Connell; Stacey E. Brenner-Moyer

doi:10.1039/d0ob01125h

Design, organocatalytic synthesis, and bioactivity evaluation of enantiopure fluorinated LpxC inhibitors

Melanie Rodríguez-Alvarado, Riccardo Russo, Nancy D. Connell, Stacey E. Brenner-Moyer

Bloomberg School of Public Health

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

Abstract

Enantiopure compounds with a strategically incorporated fluorine atom intended to enhance LpxC inhibition have been synthesized using an organocascade fluorination reaction as the key step. These are the first low molecular weight LpxC inhibitors to contain a fluorine atom on a critically important chiral center that is substituted with two pharmacophoric moieties, and were thusly designed to provide new SAR data for this class of compounds. Fluorinated compounds were evaluated against ESKAPE pathogens and exhibited MICs of ≤12.5 μg mL-1 against Pseudomonas aeruginosa.

Original language	English (US)
Pages (from-to)	5867-5878
Number of pages	12
Journal	Organic and Biomolecular Chemistry
Volume	18
Issue number	30
DOIs	https://doi.org/10.1039/d0ob01125h
State	Published - Aug 14 2020

ASJC Scopus subject areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

Access to Document

10.1039/d0ob01125h

Cite this

@article{1d2e76adab1b494482d05c4f335a255e,

title = "Design, organocatalytic synthesis, and bioactivity evaluation of enantiopure fluorinated LpxC inhibitors",

abstract = "Enantiopure compounds with a strategically incorporated fluorine atom intended to enhance LpxC inhibition have been synthesized using an organocascade fluorination reaction as the key step. These are the first low molecular weight LpxC inhibitors to contain a fluorine atom on a critically important chiral center that is substituted with two pharmacophoric moieties, and were thusly designed to provide new SAR data for this class of compounds. Fluorinated compounds were evaluated against ESKAPE pathogens and exhibited MICs of ≤12.5 μg mL-1 against Pseudomonas aeruginosa.",

author = "Melanie Rodr{\'i}guez-Alvarado and Riccardo Russo and Connell, {Nancy D.} and Brenner-Moyer, {Stacey E.}",

note = "Funding Information: This work was supported by the New Jersey Health Foundation (Grant # PC 72-19; S. E. B.-M.) and Rutgers University (S. E. B.-M.). We also thank Dr Furong Sun (University of Illinois) for the acquisition of mass spectrometry data. Publisher Copyright: {\textcopyright} The Royal Society of Chemistry.",

year = "2020",

month = aug,

day = "14",

doi = "10.1039/d0ob01125h",

language = "English (US)",

volume = "18",

pages = "5867--5878",

journal = "Organic and Biomolecular Chemistry",

issn = "1477-0520",

publisher = "Royal Society of Chemistry",

number = "30",

}

TY - JOUR

T1 - Design, organocatalytic synthesis, and bioactivity evaluation of enantiopure fluorinated LpxC inhibitors

AU - Rodríguez-Alvarado, Melanie

AU - Russo, Riccardo

AU - Connell, Nancy D.

AU - Brenner-Moyer, Stacey E.

N1 - Funding Information: This work was supported by the New Jersey Health Foundation (Grant # PC 72-19; S. E. B.-M.) and Rutgers University (S. E. B.-M.). We also thank Dr Furong Sun (University of Illinois) for the acquisition of mass spectrometry data. Publisher Copyright: © The Royal Society of Chemistry.

PY - 2020/8/14

Y1 - 2020/8/14

N2 - Enantiopure compounds with a strategically incorporated fluorine atom intended to enhance LpxC inhibition have been synthesized using an organocascade fluorination reaction as the key step. These are the first low molecular weight LpxC inhibitors to contain a fluorine atom on a critically important chiral center that is substituted with two pharmacophoric moieties, and were thusly designed to provide new SAR data for this class of compounds. Fluorinated compounds were evaluated against ESKAPE pathogens and exhibited MICs of ≤12.5 μg mL-1 against Pseudomonas aeruginosa.

AB - Enantiopure compounds with a strategically incorporated fluorine atom intended to enhance LpxC inhibition have been synthesized using an organocascade fluorination reaction as the key step. These are the first low molecular weight LpxC inhibitors to contain a fluorine atom on a critically important chiral center that is substituted with two pharmacophoric moieties, and were thusly designed to provide new SAR data for this class of compounds. Fluorinated compounds were evaluated against ESKAPE pathogens and exhibited MICs of ≤12.5 μg mL-1 against Pseudomonas aeruginosa.

UR - http://www.scopus.com/inward/record.url?scp=85089206542&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85089206542&partnerID=8YFLogxK

U2 - 10.1039/d0ob01125h

DO - 10.1039/d0ob01125h

M3 - Article

C2 - 32671374

AN - SCOPUS:85089206542

SN - 1477-0520

VL - 18

SP - 5867

EP - 5878

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

IS - 30

ER -

Design, organocatalytic synthesis, and bioactivity evaluation of enantiopure fluorinated LpxC inhibitors

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this