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 Citations (Scopus)

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

Fingerprint

Garcinia
Xanthones
Diels-Alder reactions
Oxygenation
oxygenation
Cycloaddition Reaction
Bioactivity
chemistry
Prenylation
rings
Biological Products
death
installing
induction
cascades
fragmentation
Cell Death
selectivity
Pharmacology
Cell death

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Biochemistry

Cite this

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

A-ring oxygenation modulates the chemistry and bioactivity of caged Garcinia xanthones. / Elbel, Kristyna M.; Guizzunti, Gianni; Theodoraki, Maria A.; Xu, Jing; Batova, Ayse; Dakanali, Marianna; Theodorakis, Emmanuel A.

In: Organic and Biomolecular Chemistry, Vol. 11, No. 20, 28.05.2013, p. 3341-3348.

Research output: Contribution to journalArticle

Elbel, KM, Guizzunti, G, Theodoraki, MA, Xu, J, Batova, A, Dakanali, M & Theodorakis, EA 2013, 'A-ring oxygenation modulates the chemistry and bioactivity of caged Garcinia xanthones', Organic and Biomolecular Chemistry, vol. 11, no. 20, pp. 3341-3348. https://doi.org/10.1039/c3ob40395e
Elbel, Kristyna M. ; Guizzunti, Gianni ; Theodoraki, Maria A. ; Xu, Jing ; Batova, Ayse ; Dakanali, Marianna ; Theodorakis, Emmanuel A. / A-ring oxygenation modulates the chemistry and bioactivity of caged Garcinia xanthones. In: Organic and Biomolecular Chemistry. 2013 ; Vol. 11, No. 20. pp. 3341-3348.
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