Determination of the Stereostructure of Pyrimidine Nucleoside Derivatives with a Combination of Various Chiroptical Methods

Abstract

The absolute configuration of pyrimidine nucleoside derivatives prepared by enantioselective reduction was determined using a combination of electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) spectroscopy in tandem with quantum chemical calculations. Such a combined approach based on a comparison of experimentally measured and theoretically simulated chiroptical properties allows reliable predictions of absolute configuration. The advantage of using more than one chiroptical method for the assignment of absolute configuration is demonstrated. The reliability of the proposed assignment was further confirmed by ECD measurements at variable temperatures and the use of Moscowitz procedure. This allowed the relative energies of the conformers obtained from the calculations to be verified, and the distribution of conformers to be estimated.

Stereochemical analysis of β‐keto sulfoxides by circular dichroism

“…In the current literature, there is a strong trend to use two or more distinct chiroptical methods for the determination of the absolute configuration of chiral molecules, having both natural and synthetic origin . In our previous works on aryl benzyl sulfoxides, we employed solely ECD.…”

“…Finally, our study attempts to clarify the necessity of the use of two (or more) different chiroptical methods for determining absolute configurations, which is at present a common tactic used by many authors . To do so, first we recorded ECD and VCD spectra in solution, and in the next step quantum‐chemical calculations of ECD and VCD spectra were carried out.…”

Chirality sensing of bioactive compounds with amino alcohol unit via circular dichroism

“…#2 of quinine (3) has a quite significant influence (~22.6%) on the Boltzmann weighted VCD spectrum compared with calculations described previously 64 for the gas phase (< 5%) using the B3LYP/aug-cc-pVDZ level. This fact, also well-known from ECD spectroscopy, 14 may be considered as a vulnerability of configurational assignments using only one chiroptical method. #1 and #2 one may see that a lot of bands have opposite signs ( Figure 6).…”

“…Many of their applications consist of their use as ligands in asymmetric synthesis to afford small heterocyclic derivatives as, for example, pyrrolidine, morpholinones, 2 or transoxazolines. [10][11][12][13][14][15][16][17][18][19][20][21][22][23] Far from it, in the recent literature, there are many trusted examples of assignments using only one chiroptical method, mainly electronic [24][25][26][27][28] or vibrational 29-34 circular dichroism (ECD, VCD, respectively). 5 As a consequence of significant biological activity and broad applicability in organic synthesis, vic-amino alcohols are an important class of organic compounds, whose absolute configuration (AC) determination is vital.…”

Complementarity of Electronic and Vibrational Circular Dichroism Spectroscopy in Structure Determination of Vic-Amino Alcohols

“…It is generally accepted that combined experimental and theoretical analysis opens much broader application opportunities for chiroptical spectroscopy by giving theoretical basis to experimental results [1][2][3][4]. Moreover, utilization of multiple (at least two) chiroptical techniques increases the confidence level of the stereochemical assignment and is nowadays considered by many authors to be the best practice [1][2][3][4][5].In this Editorial, we will focus on such a combined experimental and theoretical approach of electronic circular dichroism (ECD), and vibrational circular dichroism (VCD) to determine the absolute configuration and conformation. We intend to demonstrate that both these chiroptical techniques are well cooperating and mutually complementary.…”