# Knowledge base: Warsaw University of Technology

Back

## The synthesis of stilbene derivatives of adenosine

### Katarzyna Janowska

#### Abstract

Introduction Angiogenesis is the process of the growth of new blood vessels from pre-existing vessels. In this very complex and tightly controlled pathway the main role is played by epithelial cells as well as by extracellular matrix (ECM) [1]. As one of the vital processes in malignant tumor development, angiogenesis is likely to be applied to the treatment of cancer. In a tumor, various signaling factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) promote the formation of new blood vessels. Due to the release of these factors by the tumor cells, the process of angiogenesis is enhanced. As a result, the tumor is being revived and metastasis becomes more likely to occur. The therapy based on the inhibition of angiogenesis by vascular targeting agents (VTA) has been investigated during the last few years. The most promising VTA are angiogenesis inhibitors (AI) and vascular disrupting agents (VDA) [3]. Research on the application of stilbene derivatives, including combretastatin derivatives, as VTA is also carried out [4]. Their conjugates with adenosine are likely to penetrate tumor more easily, case the process of angiogenesis or disrupt the existing vessels [5]. Results and discussion The aim of the thesis was to synthesize two new stilbenes, namely (E)-2-(2-(naphtalen-1-yl)vinyl)-5-nitroaniline and (E)-3’,4’,5’-trimethoxy-2-amino-4-nitrostilbene which were next to be transformed into their iodine derivatives. Because of the deviations in N-H bond angles in the amine group (34,0o (H-N-C2-C1) and 33,8o (H-N-C2-C1) from the phenyl ring), overlapping between nitrogen lone pair electrons and ring electrons was decreased. As a consequence, some problems with the diazotization reaction occurred. Its yield was unsatisfactory and isolation of the pure products caused difficulties. Due to this fact, after running pilot reactions of halogen derivatives of benzene with adenosine (in order to optimize the conditions) 4’-bromo-2,4-dinitrostilbene was conjugated with adenosine in Ullmann-Goldberg reaction. Products were characterized by spectroscopic methods. It is also planned to investigate the biological effects of the synthesized derivatives including the impact they have on various types of living cells. Conclusions By means of aldol condensation of 2,4-dinitrotoluene and 1-naphtaldehyde or 3,4,5-trimethoxybenzaldehyde dissolved in pyrrolidine, it was possible to obtain selectively the (E) isomers of the respective derivatives of 2,4-dinitrostilbene. Selective reduction of this products lead to the respective amine with only the nitro group in the 2 (orto) position being reduced. Classic diazotization of amine derivatives of stilbenes causes problems as N-H bond angles are distorted from the ring plane, which is likely to decrease the overlapping of the lone pair electrons of amine nitrogen and the ring electrons. It is assumed that this effect leads to decreasing the activity of the amino group in the diazotization reaction. While blocking hydroxyl groups of adenosine, C6 amino group also becomes blocked. By the Ullmann-Goldberg reaction of unprotected adenosine with halogen derivatives of phenyls or stilbenes in the presence of DMEDA, copper iodide and potassium carbonate with DMSO:H2O system as a solvent, it is possible to obtain phenyl/stilbene derivatives of adenosine. [1] Mizia-Malarz, A.; Sobol, G.; Woś, H.; Pol. Merk. Lek., 2008, XXIV, 141, 185-189. [2] Rusiecka, E.; Drożdż, J.; Pol. Przegl. Kardiol., 2005, 7 (4), 351-358. [3] Horsman, R. M.; Bohn, A. B.; Busk, M.; Exp Oncol, 2010, 32, 3, 143-148. [4] Tozer, G. M.; Kanthou, C.; Baguley, B. C.; Nature Reviews, 2005, 5, 423-435. [5] Lippert, J. W.; Bioorg. Med. Chem., 2007, 15, 605-615.
Record ID
WUT8bcc55da06c8443aa53d818ff0f2df23
Diploma type
Master of Science
Author
Katarzyna Janowska Katarzyna Janowska,, Undefined Affiliation
Title in Polish
Supervisor
Hanna Krawczyk (FC/COCh) Hanna Krawczyk,, Chair of Organic Chemistry (FC/COCh)Faculty of Chemistry (FC)
Certifying unit
Faculty of Chemistry (FC)
Affiliation unit
Department Of Organic Chemistry (FC/COCh)
Study subject / specialization
, Biotechnologia Chemiczna - Leki i Kosmetyki
Language
(pl) Polish
Status
Finished
Defense Date
04-07-2012
Issue date (year)
2012
Keywords in Polish
-
Keywords in English
-
Abstract in Polish
urn:pw-repo:WUT8bcc55da06c8443aa53d818ff0f2df23