METHODS FOR BETULIN PURIFICATION: A REVIEW
DOI:
https://doi.org/10.53002/168Ключевые слова:
betulin; Betula spp.; birch bark; pentacyclic triterpenoids; isolation; purification; solvent extraction; recrystallization.Аннотация
Betulin, a pentacyclic triterpenoid abundant in the outer bark of Betula species, represents a valuable natural compound for pharmaceutical, biomedical, and cosmetic applications. Its further utilization, however, requires reliable technologies capable of providing material with a consistently high level of purity. This review examines current strategies for recovering and purifying betulin from birch bark, with emphasis on the relationship between physicochemical properties of the compound and the efficiency of individual separation processes. Solvent-based extraction, recrystallization, chromatographic procedures, and alternative purification techniques are discussed with consideration of solvent polarity, temperature-dependent solubility, hydrogen-bonding interactions, and crystalline solvate formation. Reported experimental procedures and patented technologies are evaluated with respect to product purity, solvent requirements, operational complexity, recovery efficiency, and prospects for technological scale-up. Methods employed for structural identification and purity control, particularly high-performance liquid chromatography and spectroscopic techniques, are also reviewed. Analysis of the published data indicates that recrystallization remains a practical route for obtaining highly purified betulin, although its effectiveness strongly depends on appropriate solvent selection and careful control of processing conditions. Differences in the composition of birch bark associated with species and geographical origin are additionally considered, with particular interest in less extensively investigated taxa such as Betula kirghisorum. The development of more selective, resource-efficient, and environmentally sustainable extraction and purification processes is expected to improve the production of high-purity betulin from renewable birch resources and expand opportunities for its subsequent chemical modification and practical application.
Библиографические ссылки
P. A. Krasutsky, “Birch bark research and development,” Natural Product Reports, vol. 23, no. 6, pp. 919–942, 2006.
S. K. Król, M. Kiełbus, A. Rivero-Müller, and A. Stepulak, “Comprehensive review on betulin as a potent anticancer agent,” Journal of Biomedicine and Biotechnology, vol. 2015, pp. 1–11, 2015.
J. J. Tang, J. G. Li, W. Qi, et al., “Inhibition of SREBP by a small molecule, betulin, improves hyperlipidemia and insulin resistance and reduces atherosclerotic plaques,” Cell Metabolism, vol. 13, no. 1, pp. 44–56, 2011.
A. Cunha and R. Batista, “Chemical strategies towards the synthesis of betulinic acid and its more potent antiprotozoal analogues,” Molecules, vol. 26, 2021.
V. Khwaza, B. A. Aderibigbe, and S. Mlala, “Pentacyclic triterpenoids with nitrogen-containing heterocyclic moiety, privileged hybrids in anticancer drug discovery,” Molecules, vol. 26, no. 9, 2021.
S. Amiri, S. Dastghaib, and M. Ahmad, “Betulin and its derivatives as novel compounds with different pharmacological effects,” Biotechnology Advances, vol. 38, 2020.
A. Al-Snafi, “The medical importance of Betula alba—An overview,” Journal of Pharmaceutical Biology, vol. 5, no. 2, pp. 99–103, 2015.
A. Hordyjewska, A. Ostapiuk, A. Horecka, and J. Kurzepa, “Betulin and betulinic acid: Triterpenoids derivatives with a powerful biological potential,” Phytochemistry Reviews, vol. 18, pp. 929–951, 2019.
P. de Mayo, Terpeny [Terpenes]. Moscow, USSR: Inostrannaya Literatura, 1963, 494 p. [In Russian].
V. I. Sharkov and I. A. Belyaevskii, “K voprosu o khimicheskom sostave drevesnoi kory. Kora berezy [On the chemical composition of tree bark: Birch bark],” Lesokhimicheskaya Promyshlennost [Forest Chemical Industry], nos. 3–4, pp. 30–33, 1932. [In Russian].
N. D. Pokhilko and N. I. Uvarova, “Izoprenoidy razlichnykh vidov roda Betula [Isoprenoids of various species of the genus Betula],” Khimiya Prirodnykh Soedinenii [Chemistry of Natural Compounds], no. 3, pp. 325–341, 1988. [In Russian].
V. I. Roshchin, N. Yu. Shabanova, and D. N. Vedernikov, “Sposob polucheniya betulina [Method for producing betulin],” Russian Federation Patent RU 2184120, Jun. 27, 2002. [In Russian].
A. N. Kislitsyn, “Ekstraktivnye veshchestva beresty: vydelenie, sostav, svoistva, primenenie [Extractives of birch bark: Isolation, composition, properties, and applications],” Khimiya Drevesiny [Wood Chemistry], no. 3, pp. 3–28, 1994. [In Russian].
P. Jaaskelainen, “Betulinol and its utilisation,” Paperi ja Puu, vol. 63, no. 10, pp. 599–603, 1981.
B. P. Nikol’skii, Ed., Spravochnik khimika. Tom 2: Osnovnye svoistva neorganicheskikh i organicheskikh soedinenii [Chemist’s Handbook. Vol. 2: Basic Properties of Inorganic and Organic Compounds]. Moscow, USSR: Khimiya, 1964, 1162 p. [In Russian].
V. A. Levdanskii, N. I. Polezhaeva, A. P. Es’kin, V. A. Vink, and B. N. Kuznetsov, “Sposob polucheniya betulina [Method for producing betulin],” Russian Federation Patent RU 2131882 C1, Jun. 20, 1999. [In Russian].
G. Zhao, W. Yan, and D. Cao, “Simultaneous determination of betulin and betulinic acid in white birch bark using RP-HPLC,” Journal of Pharmaceutical and Biomedical Analysis, vol. 43, no. 3, pp. 959–962, 2007.
C. Reichardt, Solvents and Solvent Effects in Organic Chemistry. Weinheim, Germany: Wiley-VCH Verlag, 2003, 469 p.
D. Cao, G. Zhao, and W. Yan, “Solubilities of betulin in fourteen organic solvents at different temperatures,” Journal of Chemical & Engineering Data, vol. 52, no. 4, pp. 1366–1368, 2007.
T. N. Drebushchak, M. A. Mikhailenko, M. E. Brezgunova, et al., “Crystal structure of betulin ethanol solvate,” Journal of Structural Chemistry, vol. 51, pp. 798–801, 2010.
M. A. Mikhailenko, T. P. Shakhtshneider, M. E. Brezgunova, et al., “Poluchenie i issledovanie fiziko-khimicheskikh svoistv sol'vatov betulina [Preparation and investigation of physicochemical properties of betulin solvates],” Khimiya Rastitel'nogo Syr'ya [Chemistry of Plant Raw Material], no. 2, pp. 63–70, 2010. [In Russian].
V. A. Yanovskii, O. S. Andrienko, V. V. Zhuk, A. A. Bakibaev, and V. I. Sachkov, “Sposob ochistki betulina [Method for purification of betulin],” Russian Federation Patent RU 2463306, Oct. 10, 2012. [In Russian].
V. V. Zhuk, V. A. Yanovskii, E. A. Yanovskaya, A. A. Bakibaev, O. S. Andrienko, Sh. M. Sharafeev, and V. I. Sachkov, “Perekristallizatsiya ekstraktov betulina iz vysokokipyashchikh uglevodorodnykh rastvoritelei [Recrystallization of betulin extracts from high-boiling hydrocarbon solvents],” Khimiya Rastitel'nogo Syr'ya [Chemistry of Plant Raw Material], no. 2, pp. 73–78, 2012. [In Russian].
S. S. Kalieva, E. A. Mamaeva, A. A. Bakibaev, et al., “Sposoby ochistki nekotorykh pentatsiklicheskikh triterpenoidov [Purification methods for some pentacyclic triterpenoids],” Bulletin of the Karaganda University. Chemistry Series, no. 2, pp. 35–39, 2017. [In Russian].
S. S. Kalieva, E. A. Mamaeva, E. Nurpeis, et al., “Spektral'nye i khromatograficheskie kharakteristiki betulina i nekotorykh ego proizvodnykh [Spectral and chromatographic characteristics of betulin and some of its derivatives],” Bulletin of L. N. Gumilyov Eurasian National University. Natural and Technical Sciences Series, no. 4, pt. 1, pp. 235–240, 2017. [In Russian].
P. Šiman, A. Filipová, A. Tichá, et al., “Effective method of purification of betulin from birch bark: The importance of its purity for scientific and medicinal use,” PLOS ONE, vol. 11, no. 5, 2016.
P. A. Krasutsky, I. V. Kolomitsyn, and D. A. Krasutskyy, “Depolymerization extraction of compounds from birch bark,” U.S. Patent 8,197,870 B2, Jun. 12, 2012.
S. A. Kuznetsova, G. P. Skvortsova, I. N. Maliar, et al., “Extraction of betulin from birch bark and study of its physico-chemical and pharmacological properties,” Russian Journal of Bioorganic Chemistry, vol. 40, no. 7, pp. 742–747, 2014.
K. M. Bhat, “Anatomy, basic density and shrinkage of birch bark,” IAWA Bulletin, vol. 3, pp. 207–211, 1982.
Загрузки
Опубликован
Как цитировать
Выпуск
Раздел
Лицензия
Copyright (c) 2026 Бакибаев А.А., Ляпунова М.В., Разгуляева Ю.Д., Салина М.В., Зайцев А.В.

Это произведение доступно по лицензии Creative Commons «Attribution-ShareAlike» («Атрибуция — На тех же условиях») 4.0 Всемирная.





