4th EucheMs chemistry congress

Poster Session 2
s1359
chem. Listy 106, s257–s1425 (2012)
Poster session 2 - organic chemistry
P - 0 9 9 4
SuBStituted
5,6-dihydro-4h-PyrroLo[1,2-B]PyrAzoLeS
L. tenorA 1 , G. JurAJ 1 , M. StAniSLAv 1 , v. AnetA 1 ,
P. MiLAn 1
1 Masaryk University Faculty of Science, Chemistry, Brno,
Czech Republic
The pyrazole based natural product - alkaloid withasomnine
was isolated from the roots of Withania somnifera, Newbouldia
laevis, the shrub Elytraria acaulis and from the stem bark of
Discopodium penninervium. Beside its analgetic effects,
withasomnine has both CNS and circulatory system depressant
properties. There are few publications related to the synthesis of
this compound.
We report here two synthetic pathways leading to substituted
5,6-dihydro-4H-pyrrolo[1,2-b] pyrazoles. The first procedure
starts with g-butyrolactone, which is transformed to
6-chlorohex-1-en-3-one alternatively in 3 or 5 steps and
in following 4 steps we are able to prepare substituted
bicyclic compounds. The last step is Suzuki coupling where we
tested different conditions changing substituted boronic acids and
various Pd-catalysts. The second route comprise thermally
initiated intramolecular cyclizations of substituted homoallenyl
azines prepared from homoallenyl aldehydes to desired
2,4-disubstituted heterocycles.
Keywords: withasomnine; pyrrolo[1; 2-b]pyrazoles; Suzuki
coupling; homoallenyl azines; intramolecular cyclization;
4 th EucheMs chemistry congress
P - 0 9 9 5
PyrroLidine iMinoSuGArS with BioLoGiCAL
ACtivity
f. teodoreSCu1 , C. StAvArAChe 1 , i. MAn1 ,
C. deLeAnu1 , L. tArKo1 , A. hirtoPeAnu1 1 “Costin D. Nenitzescu” Center of Organic Chemistry
Romanian Academy, Organic Chemistry, Bucharest, Romania
Pyrrolidine iminosugars are sugar analogs (furanoside form)
with the endocyclic oxygen replaced by a nitrogen atom, initially
known as potent glycosidase inhibitors. They have also been
found to be inhibitors of other glycoprocessing enzymes widening
the area of their medical applications (drugs for metabolic
disorders, antiviral and anticancer agents). Iminosugars are
therefore of growing interest as new therapeutic leads.
Preparation of pyrrolidine iminosugars is challenging,
involving multistep procedures with low yields and poor
stereoselectivities and this is the reason why there are no
systematic studies on the effect of stereochemistry change at the
chiral centers in the iminosugar ring. So, new methods are
required for fast access to a series of these valuable biologically
active compounds with systematic structural or stereochemical
changes in order to determine a structure – activity relationship.
The synthesis of pyrrolidine iminosugars by green and more
efficient methods involving the use of microwave and/or
ultrasonic activation will be presented, as well as the
characterization of the synthesized compounds.
The most active iminosugars to be synthesized were
identified with the in-house designed QSAR software: PRECLAV
(Property Evaluation by Class Variables) based on a calibration
set for which the biological activity was reported in literature.
Keywords: pyrrolidine iminosugars; qsar software;
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc