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

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.

disaccharide nucleosides, poly(ADP-ribose), glycosylation, optimization.

1. Efimtseva E.V., Kulikova I.V., Mikhailov S.N. Disaccharide nucleosides and their incorporation into oligonucleotides // Curr. Org. Chem. 2007. V. 11. P. 337-354.

2. Hassa P.O., Haenni S.S., Elser M., Hottiger M.O. Nuclear ADP-ribosylation reactions in mammalian cells: Where are we today and where are we going? // Microbiol. Mol. Biol. Rev. 2006. V. 70. P. 789-829.

3. Ефимцева Е.В., Михайлов С.Н. Дисахаридные нуклеозиды // Успехи химии. 2004. Т. 73. № 4. С. 435-448.

4. Ferraris D.V. Evolution of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors. From concept to clinic // J. Med. Chem. 2010. V. 53. P. 4561-4584.

5. Mikhailov S.N., Kulikova I.V., Nauwelaerts K., Herdewijn P. Synthesis of 2¢-O-α-D-ribofuranosyl-adenosine, monomeric unit of poly(ADP-ribose) // Tetrahedron. 2008. V. 64. P. 2871-2876.

6. Mikhailov S.N., Efimtseva E.V., Rodionov A.A., Bobkov G.V., Kulikova I.V., Herdewijn P. Synthesis of 2'-O-β-D-ribofuranosylnucleosides // Curr. Protocols in Nucl. Acid Chem. 2006. Suppl. 27. P. 1.14.1-1.14.19.

7. Drenichev M.S., Kulikova I.V., Bobkov G.V., Tararov V.I., Mikhailov S.N. A new protocol for selective cleavage of acyl protecting groups in 2'-O-modified 3',5'-O-(tetraisopropyldisiloxane-1,3-diyl)-ribonucleosides // Synthesis. 2010. V. 22. P. 3827-3834.

8. Кафаров В.В. Методы кибернетики в химии и химической технологии. - М.: Химия, 1971. С. 210-214.

9. Лисицын Н.В., Викторов В.К., Кузичкин Н.В. Химико-технологические системы: оптимизация и ресурсосбережение. - СПб.: Менделеев, 2007. С. 118-122.

10. Markiewicz W.T. Tetraisopropyldisiloxane-1,3-diyl a group for simultaneous protection of 3- and 5-hydroxy functions of nucleosides // J. Chem. Res. 1979. P. 24-25.