Skip to main content
SpringerLink
Log in

Isosteviol preparation and inclusion complexation of it with γ-cyclodextrin

  • Original Article
  • Published:
Journal of Inclusion Phenomena and Macrocyclic Chemistry Aims and scope Submit manuscript

Abstract

Isosteviol (Ist), a tetracyclic diterpenoid along with its structural derivatives, have received considerable attention due to its broad biological activities. Because of its low natural abundance, large scale utility of Ist has been limited. The present study described a method of preparing Ist using the typical Lewis acid approach, and the properties of its inclusion complex, namely γ-cyclodextrin/isosteviol (γ-CD/Ist), were also evaluated. Firstly, Ist was prepared from stevioside with Lewis acid. Fe3+ was the optimal catalyst and complete conversion of stevioside with a yield of 83.2% of Ist were obtained. To improve Ist aqueous solubility, γ-CD/Ist complexation was investigated. Results showed that aqueous solubility of Ist increased by 185-fold with an 1:1 γ-CD/Ist inclusion complex. At the ambient temperature, γ-CD/Ist complex aqueous solution maintained relatively unchanged at neutral and slightly higher pH values after 30 days. To our knowledge, the present study was the first such an effort on the preparation of Ist using Lewis acid and improvement of its solubility through γ-CD inclusion complex.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Ullah, A., Munir, S., Mabkhot, Y., Badshah, S.L.: Bioactivity profile of the diterpene isosteviol and its derivatives. Molecules 24(4), 678 (2019)

    Article  CAS  PubMed Central  Google Scholar 

  2. Malki, A., El-Sharkawy, A., El Syaed, M., Bergmeier, S.: Antitumor activities of the novel isosteviol derivative 10c against liver cancer. Anticancer Res. 37(4), 1591–1601 (2017)

    Article  CAS  PubMed  Google Scholar 

  3. Liu, C.J., Zhang, T., Yu, S.L., Dai, X.J., Wu, Y., Tao, J.C.: Synthesis, cytotoxic activity, and 2D-and 3D-QSAR studies of 19-carboxyl-modified novel isosteviol derivatives as potential anticancer agents. Chem. Biol. Drug Des. 89(6), 870–887 (2017)

    Article  CAS  PubMed  Google Scholar 

  4. Liu, C.J., Yu, S.L., Liu, Y.P., Dai, X.J., Wu, Y., Li, R.J., Tao, J.C.: Synthesis, cytotoxic activity evaluation and HQSAR study of novel isosteviol derivatives as potential anticancer agents. Eur. J. Med. Chem. 115, 26–40 (2016)

    Article  CAS  PubMed  Google Scholar 

  5. Huang, T.J., Chou, B.H., Lin, C.W., Weng, J.H., Chou, C.H., Yang, L.M., Lin, S.J.: Synthesis and antiviral effects of isosteviol-derived analogues against the hepatitis B virus. Phytochemistry 99, 107–114 (2014)

    Article  CAS  PubMed  Google Scholar 

  6. Huang, T.J., Yang, C.L., Kuo, Y.C., Chang, Y.C., Yang, L.M., Chou, B.H., Lin, S.J.: Synthesis and anti-hepatitis B virus activity of C4 amide-substituted isosteviol derivatives. Future Med Chem 23(4), 720–728 (2015)

    CAS  Google Scholar 

  7. Abdullah, A.-D.N., Valan, A.M., Rejiniemon, T.S.: In vitro antibacterial, antifungal, antibiofilm, antioxidant, and anticancer properties of isosteviol isolated from endangered medicinal plant pittosporum tetraspermum. Evid-Based Compl. Alt. 2015, 164261 (2015)

    Google Scholar 

  8. Khaybullin, R.N., Liang, X., Cisneros, K., Qi, X.: Synthesis and anticancer evaluation of complex unsaturated isosteviol-derived triazole conjugates. Future Med. Chem. 7(18), 2419–2428 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Zhang, H., Sun, X., Xie, Y., Zan, J., Tan, W.: Isosteviol sodium protects against permanent cerebral ischemia injury in mice via inhibition of NF-κB-mediated inflammatory and apoptotic responses. J. Stroke Cerebrovasc. 26(11), 2603–2614 (2017)

    Article  Google Scholar 

  10. Hu, H., Sun, X., Tian, F., Zhang, H., Liu, Q., Tan, W.: Neuroprotective effects of isosteviol sodium injection on acute focal cerebral ischemia in rats. Oxid. Med. Cell Longev. 2016, 1–10 (2016)

    Google Scholar 

  11. Xu, D., Xu, M., Lin, L., Rao, S., Wang, J., Davey, A.K.: The effect of isosteviol on hyperglycemia and dyslipidemia induced by lipotoxicity in rats fed with high-fat emulsion. Life Sci. 90(1–2), 30–38 (2012)

    Article  CAS  PubMed  Google Scholar 

  12. Urban, J.D., Carakostas, M.C., Taylor, S.L.: Steviol glycoside safety: are highly purified steviol glycoside sweeteners food allergens? Food Chem. Toxicol. 75, 71–78 (2015)

    Article  CAS  PubMed  Google Scholar 

  13. Koubaa, M., Rosello-Soto, E., Sic Zlabur, J., Rezek Jambrak, A., Brncic, M., Grimi, N., Boussetta, N., Barba, F.J.: Current and new insights in the sustainable and green recovery of nutritionally valuable compounds from Stevia rebaudiana Bertoni. J. Agric. Food Chem. 63(31), 6835–6846 (2015)

    Article  CAS  PubMed  Google Scholar 

  14. Gasmalla, M.A.A., Yang, R.J., Hua, X.: Stevia rebaudiana Bertoni: an alternative sugar replacer and its application in food industry. Food Eng Rev 6(4), 150–162 (2014)

    Article  CAS  Google Scholar 

  15. Avent, A.G., Hanson, J.R., Deoliveira, B.H.: Hydrolysis of the diterpenoid glycoside, stevioside. Phytochemistry 29(8), 2712–2715 (1990)

    Article  CAS  Google Scholar 

  16. Chen, J., Sun, M., Cai, J., Cao, M., Zhou, W., Ji, M.: The synthesis and crystal structure of (4α,8β,13β,16β)-13-methyl-16,18-diol-17-norkaurane: a simultaneous reduction product of isosteviol. J. Chem. Crystallogr. 41(4), 519–522 (2011)

    Article  CAS  Google Scholar 

  17. Milagre, H.M., Martins, L.R., Takahashi, J.A.: Novel agents for enzymatic and fungal hydrolysis of stevioside. Braz. J. Microbiol. 40(2), 367–372 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Lohoelter, C., Weckbecker, M., Waldvogel, S.R.: (-)-Isosteviol as a versatile ex-chiral-pool building block for organic chemistry. Eur. J. Org. Chem. 2013(25), 5539–5554 (2013)

    Article  CAS  Google Scholar 

  19. Pang, S., Ma, C., Zhang, N., He, L.: Investigation of the solubility enhancement mechanism of rebaudioside D using a solid dispersion technique with potassium sorbate as a carrier. Food Chem. 174, 564–570 (2015)

    Article  CAS  PubMed  Google Scholar 

  20. Lu, T., Xia, Y.M.: Transglycosylation specificity of glycosyl donors in transglycosylation of stevioside catalysed by cyclodextrin glucanotransferase. Food Chem. 159, 151–156 (2014)

    Article  CAS  PubMed  Google Scholar 

  21. Wan, H.D., Xia, Y.M.: Enzymatic transformation of stevioside using a β-galactosidase from Sulfolobus sp. Food Funct. 6(10), 3291–3295 (2015)

    Article  CAS  PubMed  Google Scholar 

  22. Musa, A., Miao, M., Zhang, T., Jiang, B.: Biotransformation of stevioside by Leuconostoc citreum SK24.002 alternansucrase acceptor reaction. Food Chem. 146, 23–29 (2014)

    Article  CAS  PubMed  Google Scholar 

  23. Lemus-Mondaca, R., Vega-Galvez, A., Zura-Bravo, L., Ah-Hen, K.: Stevia rebaudiana Bertoni, source of a high-potency natural sweetener: a comprehensive review on the biochemical, nutritional and functional aspects. Food Chem. 132(3), 1121–1132 (2012)

    Article  CAS  PubMed  Google Scholar 

  24. Liu, G., Yuan, Q., Hollett, G., Zhao, W., Kang, Y., Wu, J.: Cyclodextrin-based host-guest supramolecular hydrogel and its application in biomedical fields. Polymer Chem. 9(25), 3436–3449 (2018)

    Article  CAS  Google Scholar 

  25. Saokham, P., Muankaew, C., Jansook, P., Loftsson, T.: Solubility of cyclodextrins and drug/cyclodextrin complexes. Molecules (2018). https://doi.org/10.3390/molecules23051161

    Article  PubMed  PubMed Central  Google Scholar 

  26. Wang, J.P., Jin, Z.Y., Xu, X.M.: γ-Cyclodextrin on enhancement of water solubility and store stability of nystatin. J. Incl. Phenom. Macrocycl. 78(1–4), 145–150 (2014)

    Article  CAS  Google Scholar 

  27. Wu, Y., Shi, R., Wu, Y.L., Holcroft, J.M., Liu, Z., Frasconi, M., Wasielewski, M.R., Li, H., Stoddart, J.F.: Complexation of polyoxometalates with cyclodextrins. J. Am. Chem. Soc. 137(12), 4111–4118 (2015)

    Article  CAS  PubMed  Google Scholar 

  28. Ohtani, K., Aikawa, Y., Fujisawa, Y., Kasai, R., Tanaka, O., Yamasaki, K.: Solubilization of steviolbioside and steviolmonoside with γ-cyclodextrin and its application to selective syntheses of better sweet glycosides from stevioside and rubusoside. Chem. Pharm. Bull. 39(12), 3172–3174 (1991)

    Article  CAS  PubMed  Google Scholar 

  29. Higuchi, T., Connors, K.A.: Phase-solubility techniques. Adv. Anal. Chem. Instr. 4, 117–212 (1965)

    CAS  Google Scholar 

  30. Wan, H-d, Ni, Y., Zhang, H.-J., Li, D., Wang, D-wJJoIP, Chemistry, M.: Enzymatic production of steviol using a commercial β-glucosidase and preparation of its inclusion complex with γ-CD. J. Incl. Phenom. Macrocycl. Chem. 93(3), 193–201 (2019)

    Article  CAS  Google Scholar 

  31. Lopez-Nicolas, J.M., Nunez-Delicado, E., Perez-Lopez, A.J., Barrachina, A.C., Cuadra-Crespo, P.: Determination of stoichiometric coefficients and apparent formation constants for β-cyclodextrin complexes of trans-resveratrol using reversed-phase liquid chromatography. J. Chromatogr. A 1135(2), 158–165 (2006)

    Article  CAS  PubMed  Google Scholar 

  32. Reyes-Reyes, M.L., Roa-Morales, G., Melgar-Fernández, R., Reyes-Pérez, H., Gómez-Oliván, L.M., Gonzalez-Rivas, N., Bautista-Renedo, J., Balderas-Hernández, P.: Chiral recognition of abacavir enantiomers by (2-hydroxy)propyl-β-cyclodextrin: UHPLC, NMR and DFT studies. J. Incl. Phenom. Macrocycl. 82(3–4), 373–382 (2015)

    Article  CAS  Google Scholar 

  33. Liao, Y., Zhang, X., Li, C., Huang, Y., Lei, M., Yan, M., Zhou, Y., Zhao, C.: Inclusion complexes of HP-β-cyclodextrin with agomelatine: preparation, characterization, mechanism study and in vivo evaluation. Carbohydr. Polym. 147, 415–425 (2016)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors were grateful to the financial support by National Natural Science Foundation of China (Grant# 81473278). We also appreciated the teachers from the State Key Lab of Food Science and Technology for kindly help with the structural characterization.

Author information

Authors and Affiliations

  1. College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, 215123, China

    Hui-da Wan & Hong-jian Zhang

  2. Affiliated Changzhou Cancer Hospital, Soochow University, Changzhou, Jiangsu, 213032, China

    Guang-zhao He

  3. School of Chemical and Material Engineering, Jiangnan University, 1800 Lihu Avenue, Wuxi, Jiangsu, 214122, China

    Hui-da Wan

Authors
  1. Hui-da Wan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guang-zhao He
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hong-jian Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hui-da Wan.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 68 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wan, Hd., He, Gz. & Zhang, Hj. Isosteviol preparation and inclusion complexation of it with γ-cyclodextrin. J Incl Phenom Macrocycl Chem 94, 65–73 (2019). https://doi.org/10.1007/s10847-019-00907-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10847-019-00907-9

Keywords

Search

Navigation