4th EucheMs chemistry congress

Poster Session 1
s1108
chem. Listy 106, s587–s1425 (2012)
Poster session 1 - organic chemistry
P - 0 4 9 3
triLoBoLide PhArMACoPhore ModifiCAtionS
t. ziMMerMAnn 1 , M. JurASeK 1 , P. drASAr 1 ,
J. hArMAthA 2
1 Institute of Chemical Technology in Prague,
Chemistry of Natural Compounds, Prague 6, Czech Republic
2 Institute of Organic Chemistry and Biochemistry,
Chemistry of Natural Compounds, Prague 6, Czech Republic
Trilobolide is a sesquiterpene lactone isolated from Laser
trilobum. This compound was previously found to play a role as
inhibitor of sarco/endoplasmic reticulum Ca2+ -ATPase activity
(SERCA) [1] . Moreover, the farmacophores of this unique
compound are known and this contribution is coming with view
on “vicinal diol” farmacophore at positions 7 and 11 of the
guaianolide skeleton. It was previously demonstrated, that the
similar diol of the structurally related compound thapsigargin can
be easily transformed to epoxide [2] . Trilobolide was transformed
to 7,11-epoxide which was used as the starting material for further
syntheses. The modifications of epoxide may well be done by
nucleophilic opening of epoxide giving corresponding hydrines.
In this work, the primary results from epoxide opening reactions
are described. It is expected that such synthetic modifications may
change the biological behaviour of such trilobolide hybrids.
Acknowledgement: This work was supported by grant number
MSM 6046137305.
references:
1. E. Kmonickova, J. Harmatha, K. Vokac, P. Kostecká,
H. Farghali and Z. Zidek, Fitoterapia 2010, 81, 1213–1219.
2. S. Broegger Christensen, I. Kjoeller Larsen, U. Rasmussen
and C. Christophersen, The Journal of Organic Chemistry
1982, 47, 649–652.
Keywords: Terpenoids; Biological activity; Synthetic design;
4 th EucheMs chemistry congress
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc