Naslov
Synthesis, structure, and biological evaluation of C-2 sulfonamido pyrimidine nucleosides

Autori
Krizmanić, Irena ; Višnjevac, Aleksandar ; Luić, Marija ; Glavaš-Obrovac, Ljubica ; Žinić, Mladen ; Žinić, Biserka

Izvornik
Tetrahedron (0040-4020) 59 (2003), 23; 4047-4057

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
ring-opening of anhydronucleosides; C-2 sulfonamido pyrimidine nucleosides; X-ray structure; in vitro antitumor activity

Sažetak
The C-2 sulfonamido pyrimidine nucleosides were prepared by opening the 2, 2’ - or 2, 3’ -bond in anhydronucleosides under nucleophilic attack of sulfonamide anions. Reaction of sodium salt of p-toluenesulfonamide or 2-(aminosulfonyl)-N, N-dimethylnicotinamide with 2, 2’ -anhydro-1-(β -D-arabinofuranosyl)cytosine gave the C-2 sulfonamido derivatives in excellent yields. Ring opening of the less reactive 2, 2’ -anhydrouridine and 2, 3’ -anhydrothymidine could be accomplished with DBU/CH3CN activation of p-toluenesulfonamide, giving moderate yields for C-2 sulfonamido derivatives. The action of acetic acid or ZnBr2/CH2Cl2 on 5-methyl-N2-tosyl-1-(2-deoxy-5-O-trityl-b-D-threo-pentofuranosyl)isocytidine led to the cleavage of both the protection group and the nucleoside bond, yielding 5-methyl-N2-tosylisocytidine as the major product. Structures of the prepared C-2 sulfonamido nucleosides were confirmed by the 1D and 2D NMR experiments, and X-ray structural analysis of 4-imino-N2-tosylamino-1-(β -D-arabinofuranosyl)pyrimidine. Both methods confirmed β - configuration and anti-conformation of the 2-sulfonamido nucleosides. Investigated compounds displayed moderate inhibition of tumor cell growth in vitro, as determined by the MTT assay using 6 different human tumor cell lines.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA