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Determination of reaction progress in synthesis of EE-3 by NMR technique

Marek Kubiszewski ,  Marcin Cybulski ,  Łukasz S. Kaczmarek 

Instytut Farmaceutyczny (PRI), Rydygiera 8, Warszawa 01-793, Poland

Abstract

Steroids, natural or synthetic organic compounds, characterized by the molecular core structure of 17 carbon atoms arranged in four fused rings, play a crucial role  in biology, chemistry and medicine.  Among the synthetic steroids of  therapeutic value, there is a large number of anti-inflammatory agents, vitamins, growth-stimulating agents, oral contraceptives and others. Steroids classified as progestogens or aromatase inhibitors are approved for use in breast cancer therapy.

Modifications in the molecular structures of steroid compounds can produce significant differences in their biological actions. The key task in the described synthesis of EE-3 anticancer drug is the activation of an unreactive 6 position in steroid skeleton. The activation can be achieved by the transformation of substrate ADD into dipyrrolidinyl intermediate EE-1.

EE_wzoryp.JPG

Due to the optimization procedures, the reaction time should be controlled. Although different analytical methods might be effective to monitor the reaction progress, the NMR technique seems to be the most relevant in our case. The well separated proton signals, matching with the substrate ADD, product EE1 and impurity ZAN, were observed in 1H NMR spectrum. It allows to apply a single spectrum data for the identification and quantity determination of the above mentioned substances in the reaction mixture.

 

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Related papers

Presentation: Poster at VII Multidyscyplinarna Konferencja Nauki o Leku, by Marek Kubiszewski
See On-line Journal of VII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2010-03-25 13:58
Revised:   2010-03-26 09:21