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Medicinal Chemistry Research

, Volume 28, Issue 4, pp 473–484 | Cite as

Total synthesis of the linear and angular 3-methylated regioisomers of the marine natural product Kealiiquinone and biological evaluation of related Leucetta sp. alkaloids on human breast cancer

  • César R. Solorio-AlvaradoEmail author
  • Velayudham Ramadoss
  • Rocío Gámez-Montaño
  • Juan R. Zapata-Morales
  • Angel J. Alonso-Castro
Original Research
  • 237 Downloads

Abstract

A straightforward, concise, and building block-scalable, seven-step total synthesis of the unnatural 3-methylated regioisomer analog of the marine alkaloid kealiiquinone is described. The construction by a regioselective way of the 4-anisyl-3-methylbenzimidazolone core of this analog, as well as the homologation of the aromatic π-system through a 4π ring opening/6π ring closure sequence for the 1,4-quinoid ring construction by using the squaric acid chemistry, are the key features of this procedure. In light that only one total synthesis of this 3-methyl-iso-kealiiquinone has been described by using a Friedel−Crafts reaction as the key step, herein, we present our pericyclic-based strategy which was successfully concluded with the aforementioned alkaloid synthesis. The biological evaluation of these unnatural derivatives was carried out on MDA-MB231 human cancer cell lines of breast. The cis-platin (CDDP) was used as a positive control of activity.

Keywords

Total synthesis Kealiiquinone Structural analogs Marine alkaloids Marine sponges Leucetta sp 

Notes

Acknowledgements

We are grateful to CONACyT (CB-2013/220836) for financial support. We acknowledge the facilities of the DCNyE, the Chemistry Department, and the National Laboratory UGCONACyT (LACAPFEM) of the University of Guanajuato for full characterization. We also thank CONACyT for fellowships to V.R.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2019_2290_MOESM1_ESM.pdf (2.5 mb)
Supplementary Information

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.División de Ciencias Naturales y Exactas, Departamento de QuímicaUniversidad de GuanajuatoGuanajuatoMexico
  2. 2.División de Ciencias Naturales y Exactas, Departamento de FarmaciaUniversidad de GuanajuatoGuanajuatoMexico

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