SYNTHESIS AND STEREODYNAMIC STUDIES OF CHIRAL AND PHARMACOLOGICALLY INTERESTING COMPOUNDS
Main researcher
: MINTAS, MLADEN (31831) Assistants
VORKAPIĆ-FURAČ, JASNA (53001)
ŠARAC-ARNERI, RUŽA (45996)
PONGRAČIĆ, MARIO (38085)
LONČAR, LINDA (187410)
RAIĆ, SILVANA (900616)
Type of research: basic Duration from: 09/01/93. to 12/31/96. Papers on project (total): 42
Papers on project quoted in Current Contents: 15
Institution name: Fakultet kemijskog inženjerstva i tehnologije, Zagreb (125) Department/Institute: Department of Organic Chemistry Address: 41000 Zagreb, Marulićev trg 20, Croatia City: 10000 - Zagreb, Croatia
Communication
Phone: 385- 1- 4552 477/ext.23
Fax: 385-1-4550725
Summary: The synthesis ot the following classes of model chiral
molecules is proposed: singly- and doubly bridged biphenyls with
heteroatoms or functional groups in the bridge, 2H-chromenes and
atropisomeric heterocyclic biaryls. The main purpose of the cited
compounds preparation is resolution of their enantiomers and study of
stereodynamic and chirooptic properties. The ultimate aim of the studies
concerned with bridged biphenyls is to develop the method to establish
configuration of molecules in solution on the basis of correlative
informations from the experimental and calculated circular dichroism and
ultraviolet spectral data. Furthermore, the synthesis of the acyclic
purine nucleoside and nucleotide analogues as well as related molecules
containing other heterocyclic ring systems is proposed. The main reason
for this novel compounds preparation is their evaluation on antiviral
and particularly anti-HIV activities.The ultimate purpose is to
establish structure activity relationship in this class of compounds in
order to find more efficacious and selective antiviral drugs. Our
studies will also be concerned with the regiospecific synthesis of
trifluoromethyl substituted dibenzosemibullvalenes. It is known on the
basis of patent literature that related representatives of this clas of
compounds possess pharmacological properties as antidepresive agents. The
reason for these novel compounds preparation is therefore their
screening on the cited activities.
Keywords: Bridged biphenyls, 2H-chromenes, atropisomeric heterocyclic biphenyls, barriers to racemization, Gibbs energy of activation, absolute configuration determination, acyclic purine nucleoside and nucleotide analogues, antiviral activities, anti- HIV drugs, dibenzosemibullvalenes, anti-depressive drugs.
Research goals: The following goals of the proposed studies are: A.
Preparation of the model chiral organic molecules: a) 2,2'-singly and
2,2',6,6'-doubly bridged biphenyls containing heteroatoms or functional
groups in the bridge; b) 2H-chromenes and c) atropisomeric heterocyclic
biaryls. The main and common aim of the preparation of suitably
substituted compounds a)-c) is to resolve their enantiomers in order to
apply optically active compounds thus obtained in stereodynamic and
chiroptical studies. In the part of research concerned with chiral bridged
biphenyls we expect that comparison between experimental and calculated
circular dichroism and ultraviolet spectral data will permit assignment
of absolute configuration. We expect in the field of chiral chromenes to
find such molecular system that will enable separation of their
enantiomers and determination of thermodynamic parameters for
racemization. The principal aim of the studies of atropisomeric
heterocyclic biaryls is determination of the unknown Gibbs energies of
activation for restricted rotation about the C-N bond; B. Synthesis of the
acyclic purine nucleoside and nucleotide analogues as well as related
molecules containing other heterocyclic ring systems. The main purpose of
these studies is evaluation of the novel compounds on antiviral and
particularly anti HIV activities. The purpose of this evaluation is to
establish structure activity relationship in this class of compounds with
the final goal to find more efficacious and selective antiviral drugs;
C. Regiospecific synthesis of trifluoromethyl substituted
dibenzosemibullvalenes. Related representatives of this class of compounds
possess on the basis of patent literature pharmacological properties as
antidepressive agents. We expect therefore that newly prepared compounds
with trifluoromethyl groups will also exert such activities. The principal
goal of these studies is to test the novel compounds on the cited
activities.
COOPERATION - PROJECTS
Name of project
: "CHIRAL HETEROCYCLYC BIARYLS AND HELICENES"
joint research project with Prof. A. Mannschreck (University of Regensburg)
within German-Croatian scientific co-operation program "Juelich" Name of institution: Institut fuer Organische Chemie, Universitaet
Regensburg City: D-93053 - Regensburg, Deutschland
Name of project
: "SYNTHESIS ENANTIOMERIC RESOLUTION,BARRIERS
TO RACEMIZATION AND ABSOLUTE CONFIGURATION OF SOME CHIRAL 2,2'-BRIDGED AND
2,2',6,6'-DOUBLY BRIDGED BIPHENYLS" joint project with Prof. J. Sandstroem
within "Royal Swedish Academy of Engineering Sciences" Name of institution: Organic Chemistry 1, Chemical Center,
University of Lund City: S-22100 - Lund, Sweden
Name of project
: > "SYNTHESIS, ENANTIOMERIC RESOLUTION, BARRIERS
TO RACEMIZATION AND ABSOLUTE CONFIGURATION OF SOME CHIRAL 2,2'-BRIDGED
AND 2,2',6,6'-DOUBLY BRIDGED BIPHENYLS" Name of institution: University of Lund, Chemical Center, Organic
Chemistry 3, City: S-22100 - Lund, Sweden
COOPERATION - INSTITUTIONS
Name of institution
: Zavod za opću i anorgansku kemiju,
Prirodoslovno-matematički fakultet, Sveučilište u Zagrebu Type of institution: University/Faculty Type of cooperation: Joint publishing of scientific papers City: 10000 - Zagreb, Croatia
Name of institution
: Institut Ruđer Bošković Type of institution: State institute Type of cooperation: Joint publishing of scientific papers City: 10000 - Zagreb, Croatia
Name of institution
: Department of Chemistry, Brown University Type of institution: University/Faculty Type of cooperation: Joint publishing of scientific papers City: 02912 - Providence, Rhode Island, USA
Name of institution
: Chemistry Department, Lousiana State
University Type of institution: University/Faculty Type of cooperation: Joint publishing of scientific papers City: LA - Baton Rouge, Lousiana, USA
Name of institution
: Pliva istraživački institut Type of institution: Economical/Production Type of cooperation: Joint publishing of scientific papers City: 10000 - Zagreb, Croatia Other information about the project.