Enzymatic synthesis of enantiomerically pure 1,2-fluorocyclopentanols and 1,2-aminofluorocyclopentanes

1Kolodiazhna, OO
Veriovka, OS
1Kolodiazhna, AO
1Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Kyiv
Dopov. Nac. akad. nauk Ukr. 2019, 7:66-74
Section: Chemistry
Language: English

Vicinal fluorocyclopentanol are valuable chiral synthetic blocks for the preparation of a number of natural and synthetic biologically active substances Racemic cis-2-fluorocyclopentanols were separated into enantiomers by the kinetically controlled transesterification with vinyl acetate in the presence of lipases in organic media, High enantioselectivity (ee > 98 %) and good yields of compounds were obtained for all substrates using Burkholderia cepacia lipase, The fluorocyclopentanols were converted into enantiomerically pure 1,2-aminofluorocyclopentanes using the Mitsunobu reaction, The enantiomeric purity of the compounds was determined by Mosher's acid derivatization method, and the absolute configurations were determined using the Kazlauskas rule.

Keywords: aminofluorocyclopentanes, biocatalysis, fluorocyclopentanols, Kazlauskas rule, lipase Burkholderia cepacia, stereochemistry

1. Eliel, E. L., Wilen, S. H.& Mander, L. N. (1994). Stereochemistry of organic compounds. Wiley: New York.
2. Sate, T., Gotoh, Y., Watanabe, M. & Fujisawa, T. (1983). Stereoselective total synthesis of (4s)-trans-β-elemenone from (S)-2-cyclopenten-1-ol. Chem. Lett., No. 10, pp. 1533-1536. doi: https://doi.org/10.1246/cl.1983.1533
3. Hayes, R. & Wallace, T. W. (1990). A simple route to methyl 5S-(benzoyloxy)-6-oxopentanoate, a key intermediate in leukotriene synthesis. Tetrahedron Lett., 31, No. 10, pp. 3355-3356. doi: https://doi.org/10.1016/S0040-4039(00)89063-2
4. Sabol, J. S. & Cregge, R. J. (1989). Conformationally restricted leukotriene antagonists. Asymmetric synthesis of some nor-leukotriene D4 analogs, Tetrahedron Lett., 30, No. 26, 3377. doi: https://doi.org/10.1016/S0040-4039(00)99249-9
5. Hu, Q.-Y., Rege, P. D. & Corey, E. J. (2004). Simple, catalytic enantioselective syntheses of estrone and desogestrel. J. Am. Chem. Soc., 126, No. 19, pp. 5984-5986. doi: https://doi.org/10.1021/ja048808x
6. Kolodiazhna, O. O., Kolodiazhna, A. O. & Kolodiazhnyi, O. I. (2013). Enzymatic preparation of (1S,2R)- and (1R,2S)-stereoisomers of 2-halocyclopentanols. Tetrahedron: Asymmetry, 24, No. 1, pp. 37-42. doi: https://doi.org/10.1016/j.tetasy.2012.11.011
7. Haufe, G. & Bruns, S. (2002). (Salen)chromium complex mediated asymmetric ring opening of meso- and racemic epoxides with different fluoride sources. Adv. Synth. Catal., 344, No. 2, pp. 165-171. doi: https://doi.org/10.1002/1615-4169(200202)344:2<165::AID-ADSC165>3.0.CO;2-1
8. Wolker, D. & Haufe, G. (2002). Synthesis of optically active vicinal fluorohydrins by lipase-catalyzed deracemization. J. Org. Chem., 67, No. 9, pp. 3015-3021. doi: https://doi.org/10.1021/jo016331r
9. Honig, H. & Seufer-Wasserthal, P. (1990). General method for the separation of enantiomeric trans-2-substituted cyclopentanols. Synthesis, No. 12, pp. 1137-1140. doi: https://doi.org/10.1055/s-1990-27115
10. Dale, J. A. & Mosher, H. S. (1973). Nuclear magnetic resonance enantiomer regents, Configurational correlations via nuclear magnetic resonance chemical shifts of diastereomeric mandelate. O-methylmandelate, and alpha,-methoxy-alpha-trifluoromethylphenylacetate (MTPA) esters. J. Am. Chem. Soc., 95, No. 2, pp. 512-519. doi: https://doi.org/10.1021/ja00783a034
11. Kazlauskas, R. J., Weissfloch, A., N. E., Rappaport, A. T. & Cuccia, L. A. (1991). A rule to predict which enantiomer of a secondary alcohol reacts faster in reactions catalyzed by cholesterol esterase, lipase from Pseudomonas cepacia, and lipase from Candida rugose. J. Org. Chem., 56, No. 10, pp. 2656-2665. doi: https://doi.org/10.1021/jo00008a016
12. Parker, D. (1991). NMR determination of enantiomeric purity. Chem. Rev., 91, 7, pp. 1441-1457. doi: https://doi.org/10.1021/cr00007a009
13. Ohtani, I., Kusumi, T., Kashman, Y. & Kakisawa, H. (1991). High-field FT NMR application of Mosher’s method. The absolute configurations of marine terpenoids. J. Am. Chem. Soc., 113, No. 11, pp. 4092-4096. doi: https://doi.org/10.1021/ja00011a006