Catalytic Sulfation of Betulin with Sulfamic Acid: Experiment and DFT Calculation.

Aleksandr S Kazachenko,Noureddine Issaoui,Aleksandr A Kondrasenko,Yuriy N Malyar,Yaroslava D Berezhnaya,Valentina S Borovkova,Marek J Wojcik,Omar Al-Dossary,Feride Akman,Anna S Kazachenko,Natalya Yu Vasilieva,Evgeniy V Elsuf’Ev,Angelina V Miroshnikova

doi:10.3390/ijms23031602

Abstract

Betulin is an important triterpenoid substance isolated from birch bark, which, together with its sulfates, exhibits important bioactive properties. We report on a newly developed method of betulin sulfation with sulfamic acid in pyridine in the presence of an Amberlyst®15 solid acid catalyst. It has been shown that this catalyst remains stable when being repeatedly (up to four cycles) used and ensures obtaining of sulfated betulin with a sulfur content of ~10%. The introduction of the sulfate group into the betulin molecule has been proven by Fourier-transform infrared, ultraviolet-visible, and nuclear magnetic resonance spectroscopy. The Fourier-transform infrared (FTIR) spectra contain absorption bands at 1249 and 835–841 cm−1; in the UV spectra, the peak intensity decreases; and, in the nuclear magnetic resonance (NMR) spectra, of betulin disulfate, carbons С3 and С28 are completely shifted to the weak-field region (to 88.21 and 67.32 ppm, respectively) with respect to betulin. Using the potentiometric titration method, the product of acidity constants K1 and K2 of a solution of the betulin disulfate H+ form has been found to be 3.86 × 10–6 ± 0.004. It has been demonstrated by the thermal analysis that betulin and the betulin disulfate sodium salt are stable at temperatures of up to 240 and 220 °C, respectively. The density functional theory method has been used to obtain data on the most stable conformations, molecular electrostatic potential, frontier molecular orbitals, and mulliken atomic charges of betulin and betulin disulfate and to calculate the spectral characteristics of initial and sulfated betulin, which agree well with the experimental data.

Highlights

Plant biomass is an important feedstock for a wide range of valuable chemicals [1–5].Catalytic processing of plant lignocellulosic biomass is an urgent task [6]
It should be noted that the activating ability of urea and its derivatives in the reactions of sulfation with sulfamic acid can be related to the presence of hydrogen bonds and their number [48–51]
It has been shown that this catalyst remains stable in multicycle tests during sulfation of betulin with sulfamic acid in pyridine

Summary

Introduction

Plant biomass is an important feedstock for a wide range of valuable chemicals [1–5].Catalytic processing of plant lignocellulosic biomass is an urgent task [6]. Plant biomass is an important feedstock for a wide range of valuable chemicals [1–5]. Birch biomass can serve as a source of various extractive substances. Birch bark is characterized by a high content of extractive substances, which include mono- and triterpenoids, hydrocarbons, alcohols, fatty and resin acids, and phenolic compounds [7–9]. Triterpene compounds represent the most important class of bioactive substances promising for use as pharmaceutical active ingredients, drugs, and phytopreparations [10–17]. The betulin content in the birch outer bark ranges within 10–35%, depending on a type of birch, an area and conditions of its growth, an age of the tree, and other factors [15,18]. In the in vitro and in vivo experiments, betulin and its derivatives exhibit the anti-inflammatory, anticonvulsant, antibacterial, antiviral, anti-HIV, antitumor, and other types of biological activity [11–17,19–23]

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