TY - JOUR
T1 - A-ring oxygenation modulates the chemistry and bioactivity of caged Garcinia xanthones
AU - Elbel, Kristyna M.
AU - Guizzunti, Gianni
AU - Theodoraki, Maria A.
AU - Xu, Jing
AU - Batova, Ayse
AU - Dakanali, Marianna
AU - Theodorakis, Emmanuel A.
PY - 2013/5/28
Y1 - 2013/5/28
N2 - 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.
AB - 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.
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U2 - 10.1039/c3ob40395e
DO - 10.1039/c3ob40395e
M3 - Article
C2 - 23563530
AN - SCOPUS:84877268562
SN - 1477-0520
VL - 11
SP - 3341
EP - 3348
JO - Organic and Biomolecular Chemistry
JF - Organic and Biomolecular Chemistry
IS - 20
ER -