OPTIMIZATION OF 2'-О-α-D-RIBOFURANOSYLADENOSINE SYNTHESIS USING THE SIMPLEX PLANNING METHOD

Abstract

Disaccharide nucleosides belong to an important group of natural compounds found in t-RNA and poly(ADPribose). They are also key elements in the structure of antibiotics and other physiologically active compounds. Poly(ADP-ribosylation) is a posttranslational modification of proteins in eukariotic cells catalyzed by poly(ADPribose)-polymerazes. The importance of poly(ADP-ribose) has been established in many cellular processes such as DNA replication, recombination and repair and cellular differentiation. The development of the synthesis of poly(ADP-ribose) and it’s components is still a challenging problem. The synthesis of 2'-O-α-D-ribofuranosyladenosine, a monomeric unit of poly(ADP-ribose) reported earlier has been improved. An important step on this way is the formation of a 2'-O-glycosidic bond between the adenosine and carbohydrate moieties. A new strategy involving glycosylation of 3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)adenosine has been suggested. Varying of the catalyst (SnCl4), nucleoside and carbohydrate relations by the simplex method allowed improving the yields in the glycosylation step from 35 to 64%. As a result, it made possible to reach a higher overall yield of 2'-O-α-D-ribofuranosyladenosine in comparison with the literature data.

Keywords

• disaccharide nucleosides, poly(adp-ribose), glycosylation, optimization.