vuzbiochemiИзвестия вузов. Прикладная химия и биотехнологияProceedings of Universities. Applied Chemistry and Biotechnology2227-29252500-1558ИРНИТУ10.21285/2227-2925-2019-9-2-212-221vuzbiochemi-192Research ArticleХИМИЧЕСКИЕ НАУКИCHEMICAL SCIENCESПочему бензилиденовая защитная группа непредпочтительна для гликозидов формилфенолов?On why benzylidene protecting groups are not effective for formylphenol glycosidesФайскановаК. М.FaiskanovaK. M.

магистрант,

г. Томск

Master Student,

Tomsk

faiskanovakseniia@mail.ruСтепановаЕ. В.StepanovaE. V.

к.х.н., старший преподаватель Исследовательской школы химических и биомедицинских технологий,

 

Ph.D. (Chemistry), Senior Lecturer, Research School of Chemistry & Applied Biomedical Sciences,

Tomsk

eline_m@mail.ruТомский политехнический университетРоссияTomsk Polytechnic UniversityRussian Federation20192809201992212221Copyright © Файсканова К.М., Степанова Е.В., 20192019Файсканова К.М., Степанова Е.В.Faiskanova K.M., Stepanova E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vuzbiochemi.elpub.ru/jour/article/view/192

Бензилиденовые защитные группы широко используются в химии углеводов, как правило, для защиты гидроксильных групп в положениях О-4, О-6 углеводного остатка. 4,6-бензилиденовая защита позволяет с той или иной степенью селективности вводить другие функциональные группы в О-2 и О-3 положения сахаров и легко удаляется из молекулы в кислых условиях. Авторами настоящей статьи ранее была предложена схема получения ацилпроизводных природного гликозида салицина (гликозида салицилового спирта) из промежуточного гликозида гелицина (гликозида салицилового альдегида). При этом альдегидная группа может быть восстановлена до спиртовой на последних этапах синтеза и не требует дополнительной защиты во время модификации углеводного остатка, поскольку не вступает в реакции ацилирования в отличие от гидроксиметиленовой группы салицина. Для временной защиты О-4 и О-6 гидроксилов гелицина было предложено использовать бензилиденовую защитную группу. Целью данной работы являлось изучение реакционной способности гликозида гелицина в реакции образования 4,6-бензилидена и установление влияющих на нее факторов. Были предприняты попытки введения бензилиденовой защитной группы в молекулу гелицина двумя способами: с использованием диметилацеталя бензальдегида и с использованием бензальдегида и хлорида цинка. В первом случае конверсии исходного гликозида не было зафиксировано, в то время как результатом второй реакции являлся продукт неустановленной структуры. При помощи квантово-химических расчетов были смоделированы возможные реакции, протекающие с использованными реагентами и было установлено, что невозможность реакции диметилацеталя бензальдегида и бензальдегида по 4,6-гидроксилам глюкозы обусловлена конкурирующей реакцией альдегидной группы самого гелицина. Причем при катализе хлоридом цинка наиболее вероятным продуктом реакции является димер гелицина. Таким образом, было установлено, что бензилиденовая защита имеет ограничение и не может быть применена в случае гликозидов, содержащих в качестве агликона ароматические альдегиды.

Benzylidene protecting groups are widely used in carbohydrate chemistry, as a rule, to protect the hydroxyl groups at O-4 and O-6 positions of the carbohydrate residue. With varying degrees of selectivity, 4,6-benzylidene protection allows introduction of other functional groups at O-2 and O-3 positions of sugars and is easily removed from the molecule under acidic conditions. We have previously proposed a scheme for obtaining acyl derivatives of natural glycoside salicin (glycoside of salicylic alcohol) from the intermediate glycoside helicin (glycoside of salicylic aldehyde). The aldehyde group can be reduced to alcohol during the final synthesis stages. Moreover, this group does not require additional protection during the modification of the carbohydrate residue, since it does not participate in acylation reactions, unlike the hydroxymethylene group of salicin. For the temporary protection of O-4 and O-6 hydroxyls of helicin, it was proposed to use a benzylidene protecting group. In this paper, we set out to study the reactivity of helicin in the reaction of 4,6-benzylidene formation, as well as to establish factors affecting such processes. Attempts were undertaken to introduce a benzylidene protecting group into a helicin molecule in two ways: using benzaldehyde dimethyl acetal, as well as using benzaldehyde and zinc chloride. In the former case, the conversion of the original glycoside was not observed, while the second reaction resulted in the product of an unidentified structure. Possible reactions occurring with the reagents applied were modelled using quantum-chemical calculations. It is found that the inability of benzaldehyde dimethyl acetal and benzaldehyde to react on 4,6 hydroxyls of glucose is explained by the competing reaction of the aldehyde group in the structure of helicin. Moreover, the catalysis with zinc chloride most likely produces a helicin dimer. Thus, it is found that benzylidene protection has certain limitations and cannot be applied in the case of glycosides containing aromatic aldehydes as the aglycone part.

гликозидысалицинприродные гликозидыгелицин46-бензилиденированиепроизводные салицинаglycosidessalicinnatural glycosideshelicin46-benzylidenationsalicin derivativesРабота выполнена при финансовой поддержке Российского фонда фундаментальных исследований № 18-33-00365.This work was financially supported by Russian fond of fundamental research project № 18-33-00365.ReferencesWuts P.G.M., Greene T.W. Greene's protective groups in organic synthesis. John Wiley & Sons, 2006. 1400 p.Wuts P.G.M., Greene T.W. Greene's protective groups in organic synthesis. John Wiley & Sons, 2006, 1400 p.Zong G., Barber E., Aljewari H., Zhou J., Hu Z., Du, Y., Shi W. Total synthesis and biological evaluation of ipomoeassin F and its unnatural 11 R-epimer // The Journal of Organic Chemistry. 2015. Vol. 80. No. 18. P. 9279–9291. DOI: 10.1021/acs.joc.5b01765Zong G., Barber E., Aljewari H., Zhou J., Hu Z., Du, Y., Shi W. Total synthesis and biological evaluation of ipomoeassin F and its unnatural 11 R-epimer. The Journal of Organic Chemistry. 2015, vol. 80, no. 18, pp. 9279–9291. DOI: 10.1021/acs. joc.5b01765Guo J., Ye X.S. Protecting groups in carbohydrate chemistry: influence on stereoselectivity of glycosylations // Molecules. 2010. Vol. 15. No. 10. P. 7235–7265. DOI: 10.3390/molecules15107235Guo J., Ye X.S. Protecting groups in carbohydrate chemistry: influence on stereoselectivity of glycosylations. Molecules. 2010, vol. 15, no. 10, pp. 7235–7265. DOI: 10.3390/molecules15107235Wang C.C., Lee J.C., Luo S.Y., Kulkarni S.S., Huang Y.W., Lee C.C., Chang K.L., Hung S.C. Regioselective one-pot protection of carbohydrates // Nature. 2007. Vol. 446. No. 7138. P. 896–899. DOI: 10.1038/nature05730Wang C.C., Lee J.C., Luo S.Y., Kulkarni S.S., Huang Y.W., Lee C.C., Chang K.L., Hung S.C. Regioselective one-pot protection of carbohydrates. Nature. 2007, vol. 446, no. 7138, pp. 896–899. DOI: 10.1038/nature05730Picard S., Bouyssou P., Chenault J. Hemisynthesis of the naturally occurring tremuloidin // Phytochem. 1992. Vol. 31. No. 8. P. 2909–2910. DOI: 10.1016/0031-9422(92)83663-JPicard S., Bouyssou P., Chenault J. Hemisynthesis of the naturally occurring tremuloidin. Phytochem. 1992, vol. 31, no. 8, pp. 2909–2910. DOI: 10.1016/0031-9422(92)83663-JShao C., Pei Y., Borg-Karlson A.K., Pei Z. Regioselective acylation of 2′-or 3′-hydroxyl group in salicin: Hemisynthesis of acylated salicins // Chemical Research in Chinese Universities. 2014. Vol. 30. Issue 5. P. 774–777. DOI: 10.1007/s40242-014-4041-yShao C., Pei Y., Borg-Karlson A.K., Pei Z. Regioselective acylation of 2′-or 3′-hydroxyl group in salicin: Hemisynthesis of acylated salicins. Chemical Research in Chinese Universities. 2014, vol. 30, issue 5, pp. 774–777. DOI: 10.1007/s40242-014-4041-yBoeckler G. A., Gershenzon J., Unsicker S. B. Phenolic glycosides of the Salicaceae and their role as anti-herbivore defenses // Phytochemistry. 2011. Vol. 72. No. 13. P. 1497–1509. DOI: https://doi.org/10.1016/j.phytochem.2011.01.038Boeckler G. A., Gershenzon J., Unsicker S. B. Phenolic glycosides of the Salicaceae and their role as anti-herbivore defenses. Phytochemistry. 2011, vol. 72, no. 13, pp. 1497–1509. DOI: https://doi.org/10.1016/j.phytochem.2011.01.038Akao T., Yoshino T., Kobashi K., Hattori M. Evaluation of salicin as an antipyretic prodrug that does not cause gastric injury // Planta medica. 2002. Vol. 68. No. 8. P. 714–718. DOI: 10.1055/s2002-33792Akao T., Yoshino T., Kobashi K., Hattori M. Evaluation of salicin as an antipyretic prodrug that does not cause gastric injury. Planta medica. 2002, vol. 68, no. 8, pp. 714–718. DOI: 10.1055/s-2002-33792Kim C.S., Subedi L., Park K.J., Kim S.Y., Choi S.U., Kim K.H., Lee K.R. Salicin derivatives from Salix glandulosa and their biological activities // Fitoterapia. 2015. Vol. 106. P. 147–152. DOI: 10.1016/j.fitote.2015.08.013Kim C.S., Subedi L., Park K.J., Kim S.Y., Choi S.U., Kim K.H., Lee K.R. Salicin derivatives from Salix glandulosa and their biological activities. Fitoterapia. 2015, vol. 106, pp. 147–152. DOI: 10. 1016/j.fitote.2015.08.013Singh A., Malhotra S., Subban R. Anti-inflammatory and analgesic agents from Indian medicinal plants // International Journal of Integrative Biology. 2008. Vol. 3. No. 1. P. 57–72.Singh A., Malhotra S., Subban R. Antiinflammatory and analgesic agents from Indian medicinal plants. International Journal of Integrative Biology. 2008, vol. 3, no. 1, pp. 57–72.Stepanova E.V., Belyanin M.L., Filimonov V.D. Synthesis of acyl derivatives of salicin, salirepin, and arbutin // Carbohydrate research. 2014. Vol. 388C. No. 1. P. 105–111. DOI: 10.1016/j.carres.2014.02.014Stepanova E.V., Belyanin M.L., Filimonov V.D. Synthesis of acyl derivatives of salicin, salirepin, and arbutin. Carbohydrate research. 2014, vol. 388C, no. 1, pp. 105–111. DOI: 10.1016/j.carres.2014.02.014Pearl I.A., Darling S.F. Studies on the leaves of the family salicaceae, III. Migration of acyl groups during isolation of glycosides from Populus grandidentata leaves // Archives of Biochemistry and Biophysics. 1963. Vol.102. P. 33–38. DOI: 10. 1016/0003-9861(63)90316-3Pearl I.A., Darling S.F. Studies on the leaves of the family salicaceae, III. Migration of acyl groups during isolation of glycosides from Populus grandidentata leaves. Archives of Biochemistry and Biophysics. 1963, vol.102, pp. 33–38. DOI: 10. 1016/0003-9861(63)90316-3de Souza T.B., Bretas A.C.O., Alves R.J., Magalhães T.F.F., Stoianoff, M.A.R. Synthesis and antifungal activity of palmitic acid-based neoglycolipids related to papulacandin D // Química Nova. 2015. Vol. 38. No. 10. P. 1282–1288. DOI: 10.5935/0100-4042.20150156de Souza T.B., Bretas A.C.O., Alves R.J., Magalhães T.F.F., Stoianoff, M.A.R. Synthesis and antifungal activity of palmitic acid-based neoglycolipids related to papulacandin D // Química Nova. 2015, vol. 38, no. 10, pp. 1282–1288. DOI: 10.59 35/0100-4042.20150156Wilson W.E., Johnson S.A., Perkins W.H., Ripley J.E. Gas-chromatographic analysis of cardiac glycosides and related compounds // Anal. Chem. 1967. Vol. 39. No. 1. P. 40–44. DOI: 10.1021/ac60245a002Wilson W.E., Johnson S.A., Perkins W.H., Ripley J.E. Gas-chromatographic analysis of cardiac glycosides and related compounds. Anal. Chem. 1967, vol. 39, no. 1, pp. 40–44. DOI: 10.1021/ac60245a002Fei G., Fan X., Ma H., Fan P., Jia Z., Ling L. Synthesis of glycosylated chrysin derivatives via ester linkers // Chemistry of Natural Compounds. 2016. Vol. 52. No. 4. P. 602–610. DOI: 10.1007/s10600-016-1721-5Fei G., Fan X., Ma H., Fan P., Jia Z., Ling L. Synthesis of glycosylated chrysin derivatives via ester linkers. Chemistry of Natural Compounds. 2016, vol. 52, no. 4, pp. 602–610. DOI: 10.1007/s10600-016-1721-5Ren B., Wang M., Liu J., Ge J., Zhang X., Dong H. Zemplén transesterification: a name reaction that has misled us for 90 years // Green Chemistry. 2015. Vol. 17. P. 1390–1394. DOI: 10.1039/C4GC02006E.Ren B., Wang M., Liu J., Ge J., Zhang X., Dong H. Zemplén transesterification: a name reaction that has misled us for 90 years. Green Chemistry. 2015, vol. 17, pp. 1390–1394. DOI: 10.1039/C4GC02006EKim K.S., Kim J.H., Lee Y.J., Lee Y.J., Park J. 2-(Hydroxycarbonyl) benzyl glycosides: a novel type of glycosyl donors for highly efficient βmannopyranosylation and oligosaccharide synthesis by latent-active glycosylation // Journal of American Chemical Society. 2001. Vol. 123. No. 35. P. 8477–8481. DOI: 10.1021/ja015842sKim K.S., Kim J.H., Lee Y.J., Lee Y.J., Park J. 2-(Hydroxycarbonyl) benzyl glycosides: a novel type of glycosyl donors for highly efficient β-mannopyranosylation and oligosaccharide synthesis by latentactive glycosylation. Journal of American Chemical Society. 2001, vol. 123, no. 35, pp. 8477–8481. DOI: 10.1021/ja015842sda Silva I.C.G., de Pontes Santos H.B., Cavalcanti Y.W., Nonaka C.F., de Sousa S.A., de Castro R.D. Antifungal Activity of Eugenol and its Association with Nystatin on Candida albicans // Pesquisa Brasileira em Odontopediatria e Clínica Integrada. 2017. Vol. 17. No. 1. P. 1–8. DOI: 10.4034/ PBOCI.2017.171.16.da Silva I.C.G., de Pontes Santos H.B., Cavalcanti Y.W., Nonaka C.F., de Sousa S.A., de Castro R.D. Antifungal Activity of Eugenol and its Association with Nystatin on Candida albicans. Pesquisa Brasileira em Odontopediatria e Clínica Integrada. 2017, vol. 17, no. 1, pp. 1–8. DOI: 10.40 34/PBOCI.2017.171.16Stepanova E.V., Nagornaya M.O., Filimonov V.D., Valiev R.R., Belyanin M.L., Drozdova A.K., Cherepanov V.N. A new look at acid catalyzed deacetylation of carbohydrates: A regioselective synthesis and reactivity of 2-O-acetyl aryl glycopyranosides // Carbohydrate Research. 2018. Vol. 458. P. 60–66. DOI: 10.1016/j.carres.2018.02.003Stepanova E.V., Nagornaya M.O., Filimonov V.D., Valiev R.R., Belyanin M.L., Drozdova A.K., Cherepanov V.N. A new look at acid catalyzed deacetylation of carbohydrates: A regioselective synthesis and reactivity of 2-O-acetyl aryl glycopyranosides. Carbohydrate Research. 2018, vol. 458, pp. 60–66. DOI: 10.1016/j.carres.2018.02.003Reyes L., Nicolás-Vázquez I., Mora-Diez N., Alvarez-Idaboy J.R. Acid-catalyzed nucleophilic additions to carbonyl groups: is the accepted mechanism the rule or an exception? // The Journal of Organic Chemistry. 2013. Vol. 78. No. 6. P. 2327–2335. DOI: 10.1021/jo302390rReyes L., Nicolás-Vázquez I., Mora-Diez N., Alvarez-Idaboy J.R. Acid-catalyzed nucleophilic additions to carbonyl groups: is the accepted mechanism the rule or an exception? The Journal of Organic Chemistry. 2013, vol. 78, no. 6, pp. 2327–2335. DOI: 10.1021/jo302390rZhang Lei, Haoran Li Yong Wang, [ingbang Hu Characterizing the structural properties of N, N-dimethylformamide-based ionic liquid: Density-functional study // Physical Chemistry B. 2007. Vol. 111. No. 37. P. 11016–11020. DOI: 10.1021/jp0749064Zhang Lei, Haoran Li Yong Wang, [ingbang Hu Characterizing the structural properties of N, N-dimethylformamide-based ionic liquid: Density-functional study. Physical Chemistry B. 2007, vol. 111, no. 37, pp. 11016–11020. DOI: 10.1021/jp0749064

The authors declare that there are no conflicts of interest present.