Variable-temperature &amp;lt;sup&amp;gt;1&amp;lt;/sup&amp;gt;H-NMR Studies on Three C-glycosylflavones Exhibiting Rotational Isomerism

Guohong Zhou,Renliang Yan

doi:10.11648/j.mc.20210901.12

Abstract

Rotational isomerism has been observed on some C-glycosyl flavonoids with special chemical strutures. It may bring rotamers arising from restricted rotation about one single bond. C-glycosyl flavonoids showed a wide range of biological activities. This emphasizes the significance to understand the conformational stability of C-glycosyl flavonoids in drug development. Three C-glycosyl flavonoids, vaccarin (1), isovitexin-2”-O-arabinoside (2) and spinosin (3), were found to exist as rotamers in the light of their featured behavior in nuclear magnetic resonance spectroscopy (NMR). Some separated signals were observed in their 1H-NMR and 13C NMR spectra. Variable-temperature (VT) 1H-NMR experiments were then conducted to study the observation and to determine their rotational energy barriers and then evaluate their conformational stability. The temperature varied from 298K to 363K and separated signals merged at high temperature. With the help of Eyring equation, the rotational energy barriers of compounds 1-3 were calculated and found much lower than 24 kcal/mol. When the energy barrier is high enough (> 24 kcal/mol) and the time scale for interconversion (halflife > 1000 s) is long enough for isolation of individual rotamers, the isomers are termed atropisomers, which thus will display axial charity. According to this standard, the compounds 1-3 may not exhibit atropisomerism and isolation of rotamers should be difficult. Their relatively low energy barriers indicate they can be developed as rapidly equilibrating mixture.

Highlights

Rotational isomer or rotamer is one of a set of conformers arising from restricted rotation about one single bond, which is due to the presence of a sufficiently large rotational barrier to make the phenomenon observable on the time scale of the experiment
C-glycosyl flavonoids 1-3 were subjected to 1H-Nuclear magnetic resonance spectroscopy (NMR) and 13C-NMR experiments at room temperature
With the 5-OH signals as markers, the 1H-NMR spectrum of vaccarin (1) in DMSO-d6 at 298 K showed that the relative proportion of the major and minor rotamers was 1.336: 1. The two rotamers of vaccarin (1) were independently detected because they were in relatively slow interconverting

Summary

Introduction

Rotational isomer or rotamer is one of a set of conformers arising from restricted rotation about one single bond, which is due to the presence of a sufficiently large rotational barrier to make the phenomenon observable on the time scale of the experiment. Our previous phytochemical studies on Vaccaria hispanica (Miller) Rauschert isolated two C-glycosyl flavonoids, vaccarin (1) and isovitexin-2”-O-arabinoside (2) (Figure 1), both of which exhibited rotational isomerism and existed as rotamers [8]. We are aimed to determine their rotational energy barriers and evaluate their conformational stability through variable-temperature (VT)

Results

Conclusion