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

Abstract

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 1H- and 13C-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. Each technique provides a unique and specific set of information. Hence, the full spectral characteristics of key intermediates obtained from the chiral pool synthesis to the finished product of RAD were summarised and compared. For a more accurate analysis, and due to the lack of reliable and reproducible reference standards for intermediate products, their vibrational analysis was supported by quantum chemical calculations based on the density functional theory (DFT) utilising the B3LYP hybrid functional and the 6-311G(d,p) basis set. Good agreement was observed between the empirical and theoretical spectra.Graphical abstractComprehensive spectral identification (ECD, NMR, FT-IR, Raman) of key intermediates of the chiral pool synthesis of radezolid. Electronic supplementary materialThe online version of this article (doi:10.1186/s13065-017-0309-x) contains supplementary material, which is available to authorized users.

Synthesis of Oxazolidinones by using Carbon Dioxide as a C1 Building Block and an Aluminium‐Based Catalyst

“…The reaction of carbon dioxide with aziridines falls into the latter category and is an efficient, atom‐economic route for the preparation of oxazolidinones, which are important heterocyclic motifs found in commercial pharmaceuticals and which have a range of other synthetic applications . For example, antimicrobials such as radezolid, linezolid and eperezolid and the antidepressant toloxatone all contain an oxazolidinone scaffold (Figure ). Hence, the development of an environmentally friendly approach for the synthesis of oxazolidinones under mild reaction conditions is highly desirable.…”

Explanation of the Formation of Complexes between Representatives of Oxazolidinones and HDAS-β-CD Using Molecular Modeling as a Complementary Technique to cEKC and NMR

“…NMR and MM as complementary methods to cEKC were used to elucidate and understand the interaction between oxazolidinones and the selected chiral selector, HDAS-β-CD. The results obtained for LIN [4,5], TED [6][7][8], RAD [9][10][11], and STD [12] have already been published by our research group.…”

“…Additionally, in order to explain the influence of the individual structural elements of the analyzed oxazolidinone analogues, LIN and TED precursors were synthesized [9,10]. The TED precursors did not require the addition of ACN to the BGE to achieve enantioseparation, unlike the TED itself, while the LIN precursors required the presence of ACN to obtain the enantioseparation, also quite unlike LIN.…”

Bioactivity‐guided isolation of anti‐inflammatory limonins from Chukrasia tabularis

“…According to the above results, the relative configuration of 1 was completed, as shown in Figure 1 . By comparing experiments and computational ECD data, the absolute configuration of 1 was finally proved, which is a suitable method for solving the absolute configuration of natural products (Michalska et al, 2017 ; Zhao et al, 2018 ). ECD spectra were calculated by systematic conformational search, geometric optimization, and time‐dependent density functional theory calculations using Gaussian‐16 software.…”