A-ring oxygenation modulates the chemistry and bioactivity of caged Garcinia xanthones

Kristyna M. Elbel, Gianni Guizzunti, Maria A. Theodoraki, Jing Xu, Ayse Batova, Marianna Dakanali, Emmanuel A. Theodorakis

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Natural products of the caged Garcinia xanthones (CGX) family are characterized by a unique chemical structure, potent bioactivities and promising pharmacological profiles. We have developed a Claisen/Diels-Alder reaction cascade that, in combination with a Pd(0)-catalyzed reverse prenylation, provides rapid and efficient access to the CGX pharmacophore, represented by the structure of cluvenone. To further explore this pharmacophore, we have synthesized various A-ring oxygenated analogues of cluvenone and have evaluated their bioactivities in terms of growth inhibition, mitochondrial fragmentation, induction of mitochondrial-dependent cell death and Hsp90 client inhibition. We found that installation of an oxygen functionality at various positions of the A-ring influences significantly both the site-selectivity of the Claisen/Diels-Alder reaction and the bioactivity of these compounds, due to remote electronic effects.

Original languageEnglish (US)
Pages (from-to)3341-3348
Number of pages8
JournalOrganic and Biomolecular Chemistry
Volume11
Issue number20
DOIs
StatePublished - May 28 2013

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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    Elbel, K. M., Guizzunti, G., Theodoraki, M. A., Xu, J., Batova, A., Dakanali, M., & Theodorakis, E. A. (2013). A-ring oxygenation modulates the chemistry and bioactivity of caged Garcinia xanthones. Organic and Biomolecular Chemistry, 11(20), 3341-3348. https://doi.org/10.1039/c3ob40395e