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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.).
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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.
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