Enzymatic resolution of 2-cycloalkylethanols

Authors

  • O. V. Kucher Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Ukraine
  • A. O. Kolodiazhna Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Ukraine
  • O. B. Smolii Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Ukraine

DOI:

https://doi.org/10.24959/ophcj.14.823

Keywords:

2-cycloalkylethanol, enzymatic catalysis, enantioselectivity, Burkholderia Cepacia Lipase, Candida Antarctica Lipase B

Abstract

Kinetic enzymatic resolution is a convenient modern method for obtaining optically pure compounds. The behaviour of 2-cyclopropyl- and 2-cyclobutyl methylcarbinols under conditions of the biocatalytic acylation reaction has been investigated. The comparative analysis of efficiency of enzymes of Burkholderia Cepacia Lipase (BCL) and Candida Antarctica Lipase B (CAL-B) in the reactions of acylation in the presence of vinyl acetate and hydrolysis in the buffer solution has been carried out. The progress of the reaction was monitored by 1H-NMR. It has been found that in 50% conversion the selectivity of enzymatic acylation of both 2-cycloalkylethanols in the presence of BCL is low and increases with increasing the cycle ring due to the small difference in size between alkyl substituents at the chiral carbon atom. By using biocatalysis (2-cyclopropyl) – and 2-cyclobutylethanols in an optically pure (ee ≥ 95%) form have been synthesized. The comparison of the results obtained with the literature data shows that reactions of enzymatic acylation and deacylation proceed in accordance with Kazlauskas rule stating the predominant acylation of (R)-enantiomer and deacylation of (R)-acetate. To study the possibilities of application of the compounds obtained as building blocks the enantioselective synthesis of both enantiomers of (2-cyclobutyl)ethylamine has been conducted using Mitsunobu reaction with hydrazoic acid at the key stage. The optical purity of the compounds studied has been determined by analyzing the 19F-NMR spectra of their derivatives obtained as a result of interaction with Mosher’s acid chloride.

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References

  1. Naumann K. Synthetic Pyrethroid Insecticides: Structure and Properties. Chemistry of Plant Protection. Heidelberg: Springer, 1990, Vol. 4, p.241.
  2. Liu H., Huang J., Wang J., Wang M., Liu M., Wang B., Guo H., Lu Y. Eur. J. Med. Chem., 2014, Vol. 86, pp.628-638.
  3. Vianello P., Botrugno O. A., Cappa A., Ciossani G., Dessanti P., Mai A., Mattevi A., Meroni G., Minucci S., Thaler F., Tortorici M., Trifiró P., Valente S., Villa M., Varasi M., Mercurio C. Eur. J. Med. Chem., 2014, Vol. 86, pp.352-363.
  4. Lim J., Taoka B., Otte R. D., Spencer K., Dinsmore C. J., Altman M. D., Chan G., Rosenstein C., Sharma S., Su H.-P., Szewczak A. A., Xu L., Yin H., Zugay-Murphy J., Marshall C. G., Young J. R. J. Med. Chem., 2011, Vol. 54, pp.7334-7349.
  5. Jaime-Figueroa S., De Vicente J., Hermann J., Jahangir A., Jin S., Kuglstatter A., Lynch S. M., Menke J., Niu L., Patel V., Shao A. Bioorg. Med. Chem. Lett., 2013, Vol. 23, pp.2522-2526.
  6. Li J., Smith D., Krishnananthan S., Hartz R. A., Dasgupta B., Ahuja V., Schmitz W. D., Bronson J. J., Mathur A., Barrish J. C., Chen B.-C. Org. Process Res. Dev., 2012, Vol. 16, pp.156-159.
  7. Park H. S., Lee H. Y., Kim Y. H., Park J. K., Zvartau E. E., Lee H. Bioorg. Med. Chem. Lett., 2006, Vol. 16, pp.3609-3613.
  8. Pat. WO 141761 (2010) // http://patentscope.wipo.int
  9. Vinogradov M. G., Kurilov D. V., Chel’tsova G. V., Ferapontov V. A., Heise G. L. Mendeleev Commun., 2003, Vol. 13, pp.124-125.
  10. Li W., Sun X., Zhou L., Hou G., Yu. S., Zhang X. J. Org. Chem., 2009, Vol. 74, pp.1397-1399.
  11. Eagon S., Kim J., Singaram B. Synthesis, 2008, №23, pp.3874-3876.
  12. César V., Bellemin-Laponnaz S., Wadepohl H., Gade L. H. Chem. Eur. J., 2005, Vol. 11, pp.2862-2873.
  13. Bradshaw C. W., Hummel W., Wong C.-H. J. Org. Chem., 1992, Vol. 57, pp.1532-1536.
  14. Matsuda T., Nakajima Y., Harada T., Nakamura K. Tetrahedron: Asymmetry, 2002, Vol. 13, pp.971-974.
  15. Ghanem A., Aboul-Enein H. Y. Tetrahedron: Asymmetry, 2004, Vol. 15, pp.3331-3351.
  16. Kucher O. V., Kolodyazhnaya A. O., Smolii O. B., Boiko A. I., Kubyshkin V. S., Mykhailyuk P. K., Tolmachev A. A. Tetrahedron: Asymmetry, 2014, Vol. 25, pp.563-567.
  17. Kazlauskas R. J., Weissfloch A. N. E., Rappaport A. T., Cuccia L. A. J. Org. Chem. 1991, Vol. 56, pp.2656-2665.
  18. Dale J. A., Mosher H. S. J. Am. Chem. Soc., 1973, Vol. 95, pp.512-519.
  19. Mitsunobu O. Synthesis, 2008, №1, pp.1-28.
  20. Pat. WO 100065 (2014) // http://patentscope.wipo.int
  21. Pietta P. G. J. Nat. Prod., 2000, Vol. 63, pp.1035-1042.
  22. Nijveldt R. J., van Nood E., van Hoorn D. E. C., Boelens P. G., van Norren K., van Leeuwen P. A. M., Am. J. Clin. Nutr., 2001, Vol. 74, pp.418-425.
  23. Maclnnes J., Nonhebel D. C., Orszulik S. T., Suckling C. J., Wrigglesworth R. J. Chem. Soc. Perkin Trans. I, 1983, Vol. 11, pp.2771-2776.
  24. Rieke R. D., Wehmeyer R. M., Wu T.-C., Ebert G. W. Tetrahedron, 1989, Vol. 45, pp.443-454.

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Published

2014-12-10

How to Cite

(1)
Kucher, O. V.; Kolodiazhna, A. O.; Smolii, O. B. Enzymatic Resolution of 2-Cycloalkylethanols. J. Org. Pharm. Chem. 2014, 12, 65-70.

Issue

Vol. 12 No. 4(48) (2014)

Section

Original Researches

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