4th EucheMs chemistry congress

Poster Session 2
s1305
chem. Listy 106, s257–s1425 (2012)
Poster session 2 - organic chemistry
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new CAtALytiC oxidAtive And therMAL
rAdiCAL CyCLizAtion APProACheS
u. JAhn 1 , f. KAfKA 1 , t. AMAtov 1 , M. hoLAn 1 ,
M. GeBAuer 1 , P. JAGtAP 1
1 Academy of Sciences of the Czech Republic, Institute of
Organic Chemistry and Biochemistry, Prague 6,
Czech Republic
For some time we have been working on oxidative tandem
approaches combining polar organometallic processes with
radical reactions. So far these reactions had to be performed using
stoichiometric amounts of ferrocenium hexafluorophosphate. [1]
Here we present the first approaches to perform these tandem
reactions catalytically in the metal oxidant.
Reactivity limitations of certain substrates in electron
transfer-induced cyclizations are overcome by performing
stoichiometric or catalytic oxygenations using TEMPO. The
resulting alkoxyamines can be transformed subsequently to
complex ring systems using thermal radical cyclizations
employing the persistent radical effect. [2]
references:
1. Recent examples:
a) U. Jahn, E. Dinca, Chem. Eur. J. 2009, 15, 58-62.
b) U. Jahn, E. Dinca, J. Org. Chem. 2010, 75, 4480-4491.
c) U. Jahn, F. Kafka, R. Pohl, P. G. Jones, Tetrahedron
2009, 65, 10917-10929.
2. Reviews:
a) H. Fischer, Chem. Rev. 2001, 101, 3581-3610.
b) A. Studer, Chem. Eur. J. 2001, 7, 1159-1164.
c) L. Tebben, A. Studer, Angew. Chem. Int. Ed. 2011, 50,
5034-5068.
d) T. Vogler, A. Studer, Synthesis 2008, 1979-1993.
Keywords: Radical reactions; Electron transfer; Cyclization;
Domino reactions;
4 th EucheMs chemistry congress
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PyrAzinAMide derivAtiveS MiCrowAve
SyntheSiS And their BioLoGiCAL evALuAtion
o. JAndoureK 1 , M. doLezAL 1 , M. KLeMentová 1 ,
M. veJSová 1 , K. KrALovA 2
1 Charles University Faculty of Pharmacy, Department of
Pharmaceutical Chemistry and Drug Control, Hradec
Kralove, Czech Republic
2 Comenius University Faculty of Natural Sciences, Institute of
Chemistry, Bratislava, Slovak Republic
According to WHO, the number of new tuberculosis cases
is falling slowly during last years. But new problems have
appeared with Mycobacterium tuberculosis strains which are
becoming more resistant to standard treatment (first line drugs as
well as second line drugs), and with HIV co-infection, which leads
to quicker spreading of the TBC infection. These complications
have become an epidemiological problem all over the world [1] .
Pyrazinamide, which belongs to the first line
antituberculotic drugs, is very applicable for chemical
modification and becomes a template for compounds being
prepared in this research project.
3-chloropyrazine-2-carboxamide was chosen as a starting
structure and was treated with a various group of aromatic amines
(using a microwave reactor with focused field). This reaction
yielded N-substituted 3-aminopyrazine-2-carboxamides.
Prepared compounds were purified using flash
chromatography and then were chemically characterized by
melting points, IR and NMR spectra, logP, logK and elemental
analysis.
Biological tests in vitro were made afterwards. It means
antimycobacterial screening (various Mycobacterium strains,
using pyrazinamide and isoniazide as standard), antibacterial and
antifungal screening (8 bacterial and 8 fungal stems, making use
of neomycin, bacitracin, penicillin G, ciprofloxacine,
phenoxymethyl penicillin, amphotericin B, voriconazole, nystatin,
and fluconazole as standards) and testing for herbicidal activity
(inhibition of the photosynthetic electron transport in spinach
chloroplasts with DCMU (Diurone ® ) as a standard – IC ). 50
A small group of prepared substances has shown herbicidal
activity, but it has not reached as good activity as standard
(IC for DCMU is 1.9 µmol/l).
50
Acknowledgement: This study was supported by the Grant Agency
of Charles University (B-CH/710312), by Ministry of Health of
Czech Republic (IGA NZ 13346) and by Ministry of Education,
Youth and Sports of Czech Republic (SVV-2012-265-001).
references:
1. Progress, WHO Global tuberculosis control report 2011,
WHO/HTM/TB/2011.16,
Accessed at: http://www.who.int/tb/publications/
/global_report/2011/gtbr11_full.pdf, April 2nd, 2012
Keywords: Pyrazinamide; Tuberculosis; Microwave;
Mycobacterium;
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc