title: Absolute Configuration Determination of a Taxol Precursor Based on Raman Optical Activity Spectra.
abstract: Enantiomeric purity of drugs is essential for their biological activity. In the present study, we investigate the performance of Raman optical activity (ROA) spectroscopy in distinguishing four possible stereoisomers of the synthetic precursor used for the production of taxol from baccatin III. Taxol is one of the best-selling medicaments used in the treatment of ovarian, lung, and breast cancers and Kaposi's sarcoma. In a low yield, it may be isolated from the bark of the Pacific yew tree (Taxus brevifolia); however, its industrial production is largely dependent on the precursor. It is shown that for reliable comparison of the experimental and computed Raman and ROA intensities a large number of conformers had to be averaged, to properly account for molecular flexibility in solution. In addition, if combined with the density functional theory computations, ROA spectra provide convenient and economic means of absolute configuration determination.
authors.affiliation: Institute of Physics, Faculty of Mathematics and Physics, Charles University , Ke Karlovu 5, 121 16 Prague 2, Czech Republic.
authors.forename: Václav
authors.identifier: 0000-0001-8161-305X
authors.initials: V
authors.lastname: Profant
authors.affiliation: Teva Czech Industries s.r.o. , Branišovská 31, 370 05 České Budějovice, Czech Republic.
authors.forename: Alexandr
authors.initials: A
authors.lastname: Jegorov
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences , Flemingovo n. 2, 166 10 Prague 6, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Bouř
authors.affiliation: Institute of Physics, Faculty of Mathematics and Physics, Charles University , Ke Karlovu 5, 121 16 Prague 2, Czech Republic.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Baumruk
mesh_terms: D001384:Azetidines / Q000737:chemistry*; D008968:Molecular Conformation; D017239:Paclitaxel / Q000737:chemistry*; D013059:Spectrum Analysis, Raman; D013237:Stereoisomerism
chemical_list: D001384:Azetidines; D017239:Paclitaxel