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Enantioseparation of flinderoles and borreverines by HPLC on Chirobiotic V and V2 stationary phases and by CE using cyclodextrin selectors

An Erratum to this article was published on 10 January 2014


Racemic mixtures of the promising anti-malarial bisindole alkoids, flinderole A–C, desmethyl flinderole C, borreverine and isoborreverine, are baseline-separated for the first time by HPLC using vancomycin-based stationary phases and partially separated by capillary electrophoresis (CE) using cyclodextrin selectors. The HPLC results compare the performance of Chirobiotic V and V2 in the polar organic and reversed phase modes and their complementary selectivity is discussed. The performance of the cyclodextrin selectors in CE, while less effective, are discussed in terms of their selectivity in normal and reversed polarity modes.

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  1. Fernandez LS, Jobling MF, Andrews KT, Avery VM (2008) Antimalarial activity of natural product extracts from Papua New Guinean and Australian plants against plasmodium falciparum. Phytother Res 22:1409–1412

    Article  Google Scholar 

  2. Fernandez LS, Buchanan MS, Carroll AR, Feng YJ, Quinn RJ, Avery VM (2009) Flinderoles A–C: antimalarial bis-indole alkaloids from flindersia species. Org Lett. doi:10.1021/ol802506n

    Google Scholar 

  3. Fernandez LS, Sykes ML, Andrews KT, Avery VM (2010) Antiparasitic activity of alkaloids from plant species of Papua New Guinea and Australia. Int J Antimicrob Agents. doi:10.1016/j.ijantimicag.2010.05.008

    Google Scholar 

  4. Dethe DH, Erande RD, Ranjan A (2011) Biomimetic total syntheses of flinderoles B and C. J Am Chem Soc. doi:10.1021/ja1116974

    Google Scholar 

  5. Vallakati R, May JA (2012) Biomimetic synthesis of the antimalarial flindersial alkaloids. J Am Chem Soc. doi:10.1021/ja301387k

    Google Scholar 

  6. Zeldin RM, Toste FD (2011) Synthesis of flinderoles B and C by a gold-catalyzed allene hydroarylation. Chem Sci. doi:10.1039/c1sc00290b

    Google Scholar 

  7. Zeldin RM (2011) Gold(I)-catalyzed cycloisomerization reactions of allenes: An exploration of ligand effects and the total synthesis of flinderole B and C. :266 pp. Dissertation Univ. of California Berkeley, CA, USA

  8. Sheu JH, Chen YK, Hong Y, Vincent L (1993) Efficient syntheses of yuehchukene and β-(dehydroprenyl)indole. J Org Chem. doi:10.1021/jo00073a044

    Google Scholar 

  9. Tillequin F, Koch M, Pousset JL, Cave A (1978) Biomimetic synthesis of borreverine and isoborreverine. J Chem Soc Chem Commun. doi:10.1039/c39780000826

    Google Scholar 

  10. Wang X, Liu Y, Nair UB, Armstrong DW, Ellis B, Williams KM (1997) Enantiomeric composition of monoterpenes in conifer resins. Tetrahedron: Asymmetry. doi:10.1016/S0957-4166(97)00600-9

    Google Scholar 

  11. Armstrong DW, Tang Y, Chen S, Zhou Y, Bagwill C, Chen J (1994) Macrocyclic antibiotics as a new class of chiral selectors for liquid chromatography. Anal Chem. doi:10.1021/ac00081a019

    Google Scholar 

  12. Beesley TE (2004) Preparative purification of basic chiral racemates. LCGC North America p.31

  13. Sztojkov-Ivanov A, Lazar L, Fulop F, Armstrong DW, Peter A (2006) Comparison of separation efficiency of macrocyclic glycopeptide-based chiral stationary phases for the LC enantioseparation of β-amino acids. Chromatographia. doi:10.1365/s10337-006-0824-8

    Google Scholar 

  14. Bosakova Z, Curinova E, Tesarova E (2005) Comparison of vancomycin-based stationary phases with different chiral selector coverage for enantioselective separation of selected drugs in high-performance liquid chromatography. J Chromatogr A. doi:10.1016/j.chroma.2005.01.017

    Google Scholar 

  15. Takacs-Novak K, Noszal B, Tokes-Kovesdi M, Szasz G (1993) Acid–base properties and proton-speciation of vancomycin. Int J Pharm. doi:10.1016/0378-5173(93)90252-B

    Google Scholar 

  16. Berthod A, Nair UB, Bagwill C, Armstrong DW (1996) Derivatized vancomycin stationary phases for LC chiral separations. Talanta. doi:10.1016/0039-9140(96)01974-1

    Google Scholar 

  17. Kosel M, Eap CB, Amey M, Baumann P (1998) Analysis of the enantiomers of citalopram and its demethylated metabolites using chiral liquid chromatography. J Chromatogr B Biomed Sci Appl. doi:10.1016/S0378-4347(98)00384-3

    Google Scholar 

  18. El Deeb S (2010) Evaluation of a vancomycin-based LC column in enantiomeric separation of atenolol: method development, repeatability study and enantiomeric impurity determination. Chromatographia. doi:10.1365/s10337-010-1548-3

    Google Scholar 

  19. Nair UB, Chang SSC, Armstrong DW, Rawjee YY, Eggleston DS, McArdle JV (1996) Elucidation of vancomycin's enantioselective binding site using its copper complex. Chirality. doi:10.1002/(SICI)1520-636X(1996)8:8<590::AID-CHIR9>3.0.CO;2-D

    Google Scholar 

  20. Advanced Separation Technologies Inc. (2004) Chirobiotic Handbook, 5th Edition

  21. Vallakati R, Smuts JP, Armstrong DW, May JA (2013) On the biosynthesis and optical activity of the flinderoles. Tetrahedron Letters. doi:10.1016/j.tetlet.2013.08.104

  22. Juvancz Z, Kendrovics RB, Ivanyi R, Szente L (2008) The role of cyclodextrins in chiral capillary electrophoresis. Electrophoresis. doi:10.1002/elps.200700657

    Google Scholar 

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We gratefully acknowledge the Welch Foundation (Y-0026) for their continued support.

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Correspondence to Daniel W. Armstrong.

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Smuts, J.P., Na, YC., Vallakati, R. et al. Enantioseparation of flinderoles and borreverines by HPLC on Chirobiotic V and V2 stationary phases and by CE using cyclodextrin selectors. Anal Bioanal Chem 405, 9169–9177 (2013).

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  • Chirobiotic V
  • HPLC
  • Bisindole alkaloids
  • CE