| Popis: |
Marinoaziridines A and B (Figure 1a) are the first chiral aziridine-containing natural products isolated from Gram-negative bacteria from marine sediment [1]. Many aziridine-containing molecules demonstrate very useful pharmacological activity including anticancer, antibacterial, antimicrobial activity, etc. strongly indicating that the presence of the aziridine ring in natural as well as synthetic molecules is essential for such activities. Due to known activity as pharmacophore, aziridine moiety attracted considerable attention to medicinal and synthetic organic chemists [2, 3]. Our research has been focused on the total synthesis of marinoaziridines A, B, and their derivatives with the determination of unknown absolute configuration and biological activity. In this communication, we report the first total synthesis of racemic marinoaziridine B. Target compound was prepared in 6 steps by conventional reactions of organic synthesis. The route begins with the synthesis of two achiral fragments, which undergo a convergent coupling reaction of the achiral sulfur ylide derived from the sulfonium salt and the corresponding aldehyde to form the chiral epoxide as the key intermediate of our strategy. Regioselective ring-opening of the epoxide with sodium azide proceeded under acidic conditions to give the azidoalcohol which was then subjected to Staudinger reaction to give the desired marinoaziridine B. The conditions of enantioseparation of newly synthesized compound on polysaccharide chiral stationary phases based on amylose and cellulose derivatives were investigated using high performance liquid chromatography and supercritical fluid cromatography to perform the isolation of the enantiomers of marinoaziridine. The obtained results showed that the Chiral ART Cellulose SC stationary phase with selector cellulose tris- (3, 5-dichlorophenylcarbamate) proved to be the best choice in the enantioseparation. |
