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CC BY-NC-ND 4.0 · SynOpen 2020; 04(03): 51-54
DOI: 10.1055/s-0040-1707242
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This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/) (2020) The Author(s)

Effective and Versatile Synthesis of Ginkgotoxin and Its 4′-O-Derivatives through Regioselective 4′-O-Alkylation and 4′-O-Chlorination of 3,5′-O-Dibenzylpyridoxine

Boshi Huang 
a   Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 800 E Leigh Street, Richmond, VA 23298, USA   Email: yzhang2@vcu.edu
,
Richmond Danso-Danquah
a   Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 800 E Leigh Street, Richmond, VA 23298, USA   Email: yzhang2@vcu.edu
b   The Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, 800 E Leigh Street, Richmond, VA 23298, USA
,
Martin K. Safo
a   Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 800 E Leigh Street, Richmond, VA 23298, USA   Email: yzhang2@vcu.edu
b   The Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, 800 E Leigh Street, Richmond, VA 23298, USA
,
Yan Zhang  ∗
a   Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 800 E Leigh Street, Richmond, VA 23298, USA   Email: yzhang2@vcu.edu
b   The Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, 800 E Leigh Street, Richmond, VA 23298, USA
› Author AffiliationsThis work was partially supported by National Institutes of Health DA024022 and DA050311 (Y.Z.).
Further Information

Publication History

Received: 23 July 2020

Accepted after revision: 03 August 2020

Publication Date:
14 August 2020 (online)

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Abstract

A regioselective synthesis of ginkgotoxin and its derivatives is described. A blocking–deblocking strategy was employed in this new methodology, which relied on selective ketal protection of the 3- and 4′-hydroxy groups of pyridoxine. The key intermediate, O-dibenzylpyridoxine, was prepared in four steps with a reasonable yield. The present synthetic route enables convenient and versatile preparation of diversified 4′-substituted pyridoxine derivatives.

Key words

ginkgotoxin - pyridoxine

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1707242.
  • Supporting Information
 

  • References and Notes

  • 1 Parra M, Stahl S, Hellmann H. Cells 2018; 7: 84
    CrossrefPubMed
  • 2 Lainé-Cessac P, Cailleux A, Allain P. Biochem. Pharmacol. 1997; 54: 863
    CrossrefPubMed
  • 3 Williams ME, Bolton WK, Khalifah RG, Degenhardt TP, Schotzinger RJ, McGill JB. Am. J. Nephrol. 2007; 27: 605
    CrossrefPubMed
  • 4 Kesel AJ. Curr. Med. Chem. 2005; 12: 2095
    CrossrefPubMed
  • 5 Pugachev MV, Shtyrlin NV, Sapozhnikov SV, Sysoeva LP, Iksanova AG, Nikitina EV, Musin RZ, Lodochnikova OA, Berdnikov EA, Shtyrlin YG. Bioorg. Med. Chem. 2013; 21: 7330
    CrossrefPubMed
  • 6 Jones DC, Alphey MS, Wyllie S, Fairlamb AH. Mol. Microbiol. 2012; 86: 51
    CrossrefPubMed
  • 7 Kimura T, Shirakawa R, Yaoita N, Hayashi T, Nagano K, Horiuchi H. FEBS Lett. 2014; 588: 3673
    CrossrefPubMed
  • 8 Gandhi AK, Desai JV, Ghatge MS, Di Salvo ML, Di Biase S, Danso-Danquah R, Musayev FN, Contestabile R, Schirch V, Safo MK. PLoS One 2012; 7: e40954
    CrossrefPubMed
  • 9 Yang DY, Shih Y, Liu HW. J. Org. Chem. 1991; 56: 2940
    Crossref
  • 10 Zhang D.-H, Bai S, Dong X.-Y, Sun Y. J. Agric. Food Chem. 2007; 55: 4526
    CrossrefPubMed
  • 11 Korytnyk W, Ikawa M. In Synthesis of Vitamin B6 Analogs, Vol. 18. Academic Press; New York: 1970: 524
    Google Scholar
  • 12 Pugachev MV, Shtyrlin NV, Sysoeva LP, Nikitina EV, Abdullin TI, Iksanova AG, Ilaeva AA, Musin RZ, Berdnikov EA, Shtyrlin YG. Bioorg. Med. Chem. 2013; 21: 4388
    CrossrefPubMed
  • 13 Baddiley J, Mathias AP. J. Chem. Soc. 1952; 2583
    Crossref
  • 14 Korytnyk W. J. Org. Chem. 1962; 27: 3724
    Crossref
  • 15 Harris SA. J. Am. Chem. Soc. 1940; 62: 3203
    Crossref
  • 16 Liu Y, Chen SN, McAlpine JB, Klein LL, Friesen JB, Lankin DC, Pauli GF. J. Nat. Prod. 2014; 77: 611
    CrossrefPubMed
  • 17 Lorenzo CD, Ceschi A, Colombo F, Frigerio G, Bianchetti MG, Lüde S, von Dechend M, Valoti E, Restani P. Toxicol. Res. 2015; 4: 922
    Crossref
  • 18 Yazarians JA, Jiménez BL, Boyce GR. Tetrahedron Lett. 2017; 58: 2258
    CrossrefPubMed
  • 19 Frater-Schröder M, Mahrer-Busato M. Bioorg. Chem. 1975; 4: 332
    Crossref
  • 20 Liu Y, Friesen JB, Klein LL, McAlpine JB, Lankin DC, Pauli GF, Chen SN. J. Chromatogr. A 2015; 1426: 248
    CrossrefPubMed
  • 21 Korytnyk W, Srivastava SC, Angelino N, Potti PG. G, Paul B. J. Med. Chem. 1973; 16: 1096
    CrossrefPubMed