Crystal structures of betulin and its derivatives
|Elwira Chrobak 1, Ewa B. Bębenek 1, Ewa Michalik 1, Maria Jastrzębska 2, Joachim Kusz 2, Stanisław Boryczka 1|
1. Department of Organic Chemistry, The Medicial University of Silesia, Jagiellońska 4, Sosnowiec 41-200, Poland
The still growing interest in betulin (1) and its derivatives results from their wide spectrum of biological activities such as: anticancer, antiviral, antibacterial or hepatoprotective properties [1-3]. The structure of 1 is based on a 30-carbon skeleton comprising of four 6-membered rings and one 5-membered ring. Betulin (1) has three available sites for simple chemical modification, namely: secondary hydroxyl group at position C-3, primary hydroxyl group C-28 and isopropenyl side chain at position C-20. These group and their positions, mutual distance and orientation with respect to the rings can influence hydrogen bonding and the interctions of betulin derivatives with active sites of surrounding species. Despite the fact that betulin has been known for over 200 years, the X-ray structure of this compound was investigated for first time by Drebushchak and Boryczka as betulin-EtOH and betulin-DMSO solvates, respectively [4,5]. Various solvent used in the crystallization process and different melting points reported may indicate the existence of several crystal polymorphic forms of betulin. It is well know, that the large numbers of natural molecules are capable of exhibiting polymorphism or solvatomorphism . More importantly, different polymorphic forms of pharmaceutical compounds display varying physicochemical properties, such as: solubility, stability, density as well as bioavailability, particularly when the drug substance is poorly soluble.
In the present work, we describe the synthesis and X-ray crystal structures of the betulinic acid (2), betulonic acid (3), betulone (4), betulonal (5) and new acetylenic derivatives of betulin (6,7) in order to gain better understanding of the structure-activity relationship of these important molecules.
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Presentation: Poster at VIII Multidyscyplinarna Konferencja Nauki o Leku, by Elwira Chrobak
See On-line Journal of VIII Multidyscyplinarna Konferencja Nauki o Leku
Submitted: 2012-04-03 09:27 Revised: 2012-04-03 12:17
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