Comprehensive spectral identification of key intermediates to the final product of the chiral pool synthesis of radezolid.

Radezolid (RAD, 12), biaryl oxazolidinone, was synthesised with small modifications according to the methods described in the literature. The pharmacological activity is observed only for (S)-enantiomer, therefore its synthesis is oriented towards obtaining a single isomer of required purity and desired optical configuration. The intermediate products of RAD synthesis were characterised using H- and C-NMR, as well as the 2D correlation HSQC and HMBC (2, 5, 9, 10), furthermore studied using infrared radiation (FT-IR), Raman scattering (3, 5, 9), and electronic circular dichroism (ECD) (5, 12) spectroscopy.

Application of spectroscopic methods (FT-IR, Raman, ECD and NMR) in studies of identification and optical purity of radezolid.

In the presented study, N-{[(5S)-3-(2-fluoro-4'-{[(1H-1,2,3-triazol-5-ylmethyl)amino]methyl}biphenyl-4-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide (radezolid) was synthesized and characterized using FT-IR, Raman, ECD and NMR. The aim of this work was to assess the possibility of applying classical spectral methods such as FT-IR, Raman, ECD and NMR spectroscopy for studies on the identification and optical purity of radezolid. The experimental interpretation of FT-IR and Raman spectra of radezolid was conducted in combination with theoretical studies.

Enantioselective recognition of radezolid by cyclodextrin modified capillary electrokinetic chromatography and electronic circular dichroism.

A method for the enantioseparation of radezolid (RAD), an analogue of a truly new class of antibacterial agents, oxazolidinones, was developed based on capillary electrokinetic chromatography using a cyclodextrin as a chiral pseudophase (CD-cEKC). The mechanism of RAD separation, together with its precursor, were investigated to directly define the relationship between the oxazolidinone structure and the complexation process. During the development of the method, anionic single isomer cyclodextrins were tested.

Chiral separation of tedizolid using charge single isomer derivatives of cyclodextrins by capillary electrokinetic chromatography.

A method to enantioseparate tedizolid (TED), the second analogue after linezolid (LIN) in a truly new class of antibacterial agents, the oxazolidinones, was developed based on capillary electrokinetic chromatography using cyclodextrin as chiral pseudophase (CD-cEKC). The single isomer R-tedizolid possesses one chiral centre at C5 of the oxazolidinone ring, which is associated with the antibacterial activity of the drug. Tedizolid enantiomers are non-charged and therefore require the use of charged cyclodextrins (CCDs) as carrier hosts to achieve a velocity difference during migration.

5,6,7,8-Tetra-hydro-quinolin-8-one.

In the quinoline fused-ring system of the title compound, C(9)H(9)NO, the pyridine ring is planar to within 0.011 (3) Å, while the partially saturated cyclo-hexene ring adopts a sofa conformation with an asymmetry parameter ΔC(s)(C6) = 1.5 (4)°.