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An alternative approach to the synthesis of anticancer molecule spirobrassinin and its 2′-amino analogues

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Abstract

A convenient synthesis of the cruciferous phytoalexin (S)-(−)-spirobrassinin and its (±)-2′-amino analogues have been achieved. Our synthetic route towards (S)-(−)-spirobrassinin is based on the CrO3-mediated cyclization of chiral 1-(2′,3′,4′,6′-tetra-O-acetyl-ß-D-glucopyranosyl)brassinin and subsequent removal of the chiral auxiliary. (±)-2′-Amino analogues of spirobrassinin and 1-methoxyspirobrassinin were obtained from thioureas in one step in an efficient manner with the aid of CrO3. New synthesized compounds were screened in vitro for antiproliferative/cytotoxic activity against six human cancer cell lines by MTT assay. Amino analogues with CF3 functionality displayed good antiproliferative effect.

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Acknowledgments

The present study was supported in part by the Grant Agency of Ministry of the Education, Science, Research and Sport of the Slovak Republic (VEGA 1/0753/17 and VEGA 1/0018/16), and the Slovak Research and Development Agency under the Contract No. APVV-16-0446. Moreover, this publication is the result of the project implementation: „Medicínsky univerzitný vedecký park v Košiciach (MediPark, Košice - Fáza II.)“, kód ITMS2014+313011D103 supported by the Operational Programme Research & Innovation, funded by the ERDF“. The authors thank Assoc. prof. D. Berkeš and Dr. J. Markus for synthesis and providing of the (R)-2-(1H-indol-3-yl)glycine.

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Correspondence to Mariana Budovská.

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Budovská, M., Tischlerová, V., Mojžiš, J. et al. An alternative approach to the synthesis of anticancer molecule spirobrassinin and its 2′-amino analogues. Monatsh Chem 151, 63–77 (2020). https://doi.org/10.1007/s00706-019-02528-x

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Keywords

  • Spirobrassinin
  • Phytoalexins
  • Oxidative spirocyclization
  • Antiproliferative activity