Design, synthesis and evaluation of the antibacterial activity of new Linezolid dipeptide-type analogues

García-Olaiz, G.D.; Alcántar-Zavala, Eleazar; Ochoa-Terán, Adrían; Cabrera, Alberto; Muñíz-Salazar, Raquel; Montes‐Ávila, Julio; Salazar-Medina, Alex J.; Alday, Efrain; Velázquez, Carlos; Medina-Franco, José L.; Laniado-Laborı́n, Rafael

doi:10.1016/j.bioorg.2019.103483

Cited by 12 publications

(10 citation statements)

References 43 publications

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“…Furthermore, we also investigated representative transformations of spiro-oxazolidinone products to showcase the versatility of this methodology. As shown in Scheme b, both the chiral and racemic 2a were successfully converted to the corresponding β-amino alcohols 5a and pharmaceutically interesting compounds 6a with good yields. , These synthetic applications further highlighted the utility and scalability of the biocatalytic ring expansion strategy.…”

Section: Resultsmentioning

confidence: 99%

Biocatalytic Construction of Spiro-Oxazolidinones via Halohydrin Dehalogenase-Catalyzed Ring Expansion of Spiro-Epoxides

Ma,

Wang,

Miao

et al. 2024

ACS Catal.

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Spiro-oxazolidinones are highly valuable compounds in the fields of medicinal and organic chemistry; however, the methods for synthesizing these compounds have not been well established. Herein, we present a biocatalytic methodology for the construction of spirooxazolidinones through the halohydrin dehalogenase-catalyzed ring expansion of spiro-epoxides. By performing screening and protein engineering of halohydrin dehalogenases, both chiral and racemic spirooxazolidinones were synthesized in 24−47% yields (90−98% ee) and 69−98% yields, respectively. The biocatalytic method was also applied to the efficient synthesis of the drug fenspiride at a high substrate concentration of 200 mM (44 g/L). In addition, a chemo-enzymatic strategy was proposed to overcome the limitation of the maximum 50% yield inherent in the kinetic resolution process. Moreover, large-scale synthesis and representative transformations of the spiro-oxazolidinones were carried out to provide additional evidence of the practicality and applicability of the biocatalytic approach.

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Section: Resultsmentioning

confidence: 99%

Biocatalytic Construction of Spiro-Oxazolidinones via Halohydrin Dehalogenase-Catalyzed Ring Expansion of Spiro-Epoxides

Ma,

Wang,

Miao

et al. 2024

ACS Catal.

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“…Chiral epoxides can be converted into diverse highly functionalized molecules via regio- and enantiospecific ring-opening reactions. − Herein, representative transformations of chiral oxazolidinones were investigated. As shown in Scheme C, chiral oxazolidinones ( R )- 3a and ( S )- 3a were smoothly converted into the pharmaceutically interesting chiral compounds ( R )- 4a and ( S )- 4a , respectively . A limitation of the biocatalytic desymmetrization strategy is that the obtained chiral epoxide and oxazolidinone products carry a chloromethyl group.…”

Section: Results and Discussionmentioning

confidence: 99%

Stereodivergent Synthesis of Epoxides and Oxazolidinones via the Halohydrin Dehalogenase-Catalyzed Desymmetrization Strategy

Huang

Wang

et al. 2022

ACS Catal.

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Catalytic stereoselective desymmetrization of prochiral compounds to valuable chiral molecules is of interest in asymmetric synthesis. Here, we report the development of an efficient biocatalytic desymmetrization strategy for the stereodivergent synthesis of various chiral epoxides and oxazolidinones by the identification and engineering of halohydrin dehalogenases. The use of stereocomplementary halohydrin dehalogenases for the desymmetrization of 2-substituted-1,3-dichloro-2-propanols generates chiral epoxides in up to 95% yield and 99% ee by a single-step dehalogenation reaction, as well as chiral oxazolidinones in up to 88% yield and >99% ee via a dehalogenation and cyanate-mediated epoxide ring-opening cascade reaction. We also propose a probable mechanism for stereoselectivity control in the halohydrin dehalogenase-catalyzed desymmetrization reaction.

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“…In order to explain the differences in antibacterial activity of the evaluated nanomaterials at the molecular level, an automated molecular docking study was performed in the Phosphoryl Transferase Center (PTC) of E. coli, which is commonly used to study drug-receptor interactions that inhibit protein synthesis in bacteria. 43,44 The structure of amino-linezolid 7, aminooligoethylene linezolid analogs (S n -7), and their protonated forms (S n -7-H + ) were modeled in the PTC.…”

Section: Molecular Docking Studiesmentioning

confidence: 99%

Synthesis of covalent bonding MWCNT-oligoethylene linezolid conjugates and their antibacterial activity against bacterial strains

et al. 2021

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Design, synthesis and evaluation of the antibacterial activity of new Linezolid dipeptide-type analogues

Cited by 12 publications

References 43 publications

Biocatalytic Construction of Spiro-Oxazolidinones via Halohydrin Dehalogenase-Catalyzed Ring Expansion of Spiro-Epoxides

Biocatalytic Construction of Spiro-Oxazolidinones via Halohydrin Dehalogenase-Catalyzed Ring Expansion of Spiro-Epoxides

Stereodivergent Synthesis of Epoxides and Oxazolidinones via the Halohydrin Dehalogenase-Catalyzed Desymmetrization Strategy

Synthesis of covalent bonding MWCNT-oligoethylene linezolid conjugates and their antibacterial activity against bacterial strains

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