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Stereoselective Approaches toward the Synthesis of Nucleoside Antibiotic Core Aminoribosyl Glycyluridine
Author(s) -
Patel Bhautikkumar,
Grant Gary,
Zunk Matthew,
Rudrawar Santosh
Publication year - 2019
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201900708
Subject(s) - pharmacophore , chemistry , nucleoside , antibiotics , translocase , combinatorial chemistry , peptidoglycan , mechanism of action , bacterial cell structure , uridine , stereochemistry , biochemistry , computational biology , enzyme , bacteria , rna , biology , gene , in vitro , genetics , chromosomal translocation
Antibiotics that have a novel mechanism of action are urgently required for treatment of drug‐resistant microorganisms. Naturally occurring nucleoside antibiotics have shown promising antibacterial activity by inhibiting bacterial translocase MraY, a key enzyme involved in catalysis of the first step of bacterial peptidoglycan biosynthesis. Despite having promising antibiotic properties, a major challenge toward development of this important class of compounds as drug candidates is their complex multistep synthesis. Specifically, efficient synthetic methodologies toward producing the aminoribosylated uridine‐derived core unit in a stereo‐controlled manner is seen as an essential prerequisite for detailed structure‐activity relationship (SAR) studies. This review summarizes approaches available for the stereoselective synthesis of nucleoside core pharmacophores, including both 5′‐ C ‐glycyluridine (GlyU) as well as it's β‐selective ribosylation.