4th EucheMs chemistry congress

Poster Session 1
s1077
chem. Listy 106, s587–s1425 (2012)
Poster session 1 - organic chemistry
P - 0 4 3 1
AntioxidAtive ACtivity of SuBStituted
5-AMinoPyriMidineS And their oxidAtive
SeLf-CondenSAtion in diMethyL SuLfoxide
e. ProCházKová 1 , A. BrezinovA 2 , P. JAnSA 2 ,
A. hoLy 2 , h. MertLiKovA-KAiSerovA 2 ,
M. drACinSKy 2
1 Charles University of Prague Faculty of Science, Department
of Physical and Macromolecular Chemistry, Prague, Czech
Republic
2 Institute of Organic Chemistry and Biochemistry AS CR, NMR,
Prague, Czech Republic
Pyrimidine heterocyclic nucleobases are the basic building
blocks of nucleic acids, but they also work as coenzymes or highenergy
molecules. Modified pyrimidines display a wide range of
biological properties such as antiviral, cytostatic or antimicrobial
activities. In this work we have observed the antioxidative effects
of a series of substituted 5-aminopyrimidines using in vitro
(TEAC, LPO) and cell-based assays. 2,4,6-trisubstituted
5-aminopyrimidines have been discovered as the most active in
the TEAC (direct scavenging of long-lived radical) and LPO
(compounds ability to protect rat liver microsomes against the
Fe2+ /O -induced lipid peroxidation) assays but not in cell-based
2
assay probably because of lower cell membrane permeability.
Hence, the compounds which contained “protected”
5-aminogroup by a lipophilic substituent actually acted like a
potential prodrugs, and the oxidative stress of Hep G2 cells was
decreased. On the other hand, in cell-free assays the antioxidative
activity of potential prodrugs was not found which is in agreement
with the fact that the presence of “free” aminogroup in position 5
on pyrimidine skeleton is necessary for the antioxidative ability
of the studied compound. Surprisingly, the active compounds
were decomposed in dimethyl sulfoxide (DMSO) to deeply
coloured and highly insoluble products. DMSO can act as an
oxidation agent, but the ability of DMSO to oxidize
5-aminopyrimidines has not been described till now. We
determined the structures of the products obtained by the DMSO
oxidation of 5-aminopyrimidines. The 5-aminogroup can be
oxidized to a keto group and a subsequent condensation with
another molecule of an aminopyrimidine leads to tricyclic
pyrimidinopteridines condensation products. The reaction rate of
the oxidation-condensation reaction correlates well with the
antioxidant activities of the 5-aminopyrimidines.
Keywords: 5-aminopyrimidines; antioxidants; lipid
peroxidation; DMSO oxidation; pyrimidopteridines;
4 th EucheMs chemistry congress
P - 0 4 3 2
A reinveStiGAtion of the reGioSeLeCtive
SyntheSiS of triMethoxyiSLAndiCin
S. quevA 1 , M. SorMAz 1 , C. vALLA 1 , e. urBAn 1 ,
B. LAChMAnn 1 , C. r. noe 1
1 University of Vienna Faculty of Life Science, Medicinal
Chemistry, Vienna, Austria
The mould metabolite islandicin [1] represents a key
substructure of anthracycline tumour antibiotics. Thus it is not
surprising that the total synthesis of this compound has been
extensively investigated, resulting in several described synthetic
methods for unsymmetrical anthraquinones. Nevertheless, there
is still a controversy [2] about reaction regiospecificity, which is
required to obtain unambiguous relative positions of the methoxy
group on the one side of the ring system and the methyl group on
the other. Our interest in an efficient industrial synthesis of
anthracyclines prompted us to reinvestigate the synthesis of
trimethoxyislandicin.
Our synthetic sequence started with 2,3-dimethylanisole,
which prove to be a superior source for 3-methoxyphthalic
anhydride. The key step of the reaction was a Friedel-Crafts
acylation of the anhydride with 2,5-dimethoxytoluene. This
reaction was studied carefully both with respect to overall
regioselectivity and yield of the desired regioisomer.
A modification of the anthraquinone ring closure was worked out,
which allowed carrying out the ring closure reaction and the
preceding reduction in one pot, followed by oxidation to yield the
title product.
references:
1. Howard B. H., Raistrick H., Biochem. J., 44, 227 (1949)
2. Smith W. C., Ambler J. S., Steggles J. D., Tetrahedron.
Lett., 34 (46), 7747-77450 (1993);
Kim K. S., Spatz M. W., Johnson F., Tetrahedron Lett., 4,
331-334 (1979);
deSilva S. O., Watanabe M., Snieckius V., J. Org. Chem.,
44 (26), 4802-4808 (1979);
Kende A. S., Belletire J. L., Herrmann J. L., Romanet R. F.,
Hume E. L., Schlessinger R. H., Syn. Commun., 3 (6),
387-392, (1973)
Keywords: Regioselectivity;
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc