1 research outputs found
Stereochemical characterization of methyl trans-3-(3,4-dimethoxyphenyl)glycidate by enantioselective HPLC-CD analysis and TD-DFT calculations
Enantiomerically pure oxiranes are valuable electrophilic, chiral synthons [1] and have been
introduced into pharmaceutical applications for the synthesis of biologically active polyethers.
Stereochemical characterization plays an important role in medicinal chemistry, since chirality is
fundamental in the definition of the activity of several biologically active compounds.
Consequently, analytical techniques allowing for the stereochemistry to be fully characterized are
receiving increasing attention. The absolute configuration of methyl trans-3-(3,4-
dimethoxyphenyl)glycidate (trans-1), a recently synthesized building block for the synthesis of
methylated analogues of biologically active polymers from different species of comfrey and
bugloss [2], was investigated by means of enantioselective high-performance liquid
chromatography hyphenated with a circular dichroism detection system (eHPLC-CD) [3]. A Lux
Cellulose-4 and a Lux Cellulose-2 columns were successfully employed for the preparative and
analytical enantioresolution of racemic trans-1 [4]. The CD spectra of the enantiomeric fractions
of trans-1 were then measured both by off-line analysis after preparative chromatographic
separation and by stopped-flow measurements during the eHPLC-CD analysis [3]. This last
strategy resulted more reliable, because the risk of degradation of the analyte was drastically
reduced. The absolute configuration of each enantiomeric fraction was finally determined by
comparison of the experimental CD spectra with quantum mechanical (QM) calculations based on
time-dependent density functional theory (TD-DFT). The conformationally-averaged theoretical
CD spectrum of (2S,3R)-1 reproduced with a reasonable degree of accuracy the CD spectrum of
the first-eluted fraction of trans-1 on the Lux Cellulose-2 column: consequently, a full
stereochemical characterization of the enantiomers of trans-1 was achieved and the elution order
on Lux Cellulose-2 was determined.
[1] H.C. Kolb, M.S. VanNieuwenhze, K.B. Sharpless, Catalytic asymmetric dihydroxylation,
Chem. Rev. 94 (1994) 2483\u20132547.
[2] V. Barbakadze, L. Gogilashvili, L. Amiranashvili, M. Merlani, K. Mulkijanyan, Novel
biologically active phenolic polymers from different species of genera Symphytum and Anchusa
(Boraginaceae), J. Chem. Eng. Chem. Res. 1 (2014) 47\u201353.
[3] C. Bertucci, D. Tedesco, Advantages of electronic circular dichroism detection for the
stereochemical analysis and characterization of drugs and natural products by liquid
chromatography, J. Chromatogr. A 1269 (2012) 69\u201381.
[4] K. Lomsadze, M. Merlani, V. Barbakadze, T. Farkas, B. Chankvetadze, Enantioseparation of
chiral epoxides with polysaccharide-based chiral columns in HPLC, Chromatographia 75 (2012)
839\u2013845