Organizing co mmittee

NEW ADENOSINE ANALOGS: CHEMICAL-ENZYMATIC 
SYNTHESIS 
 
Maria Ya. Berzina, Alexey L. Kayushin, Elena V. Dorofeeva, Olga I. Lutonina, 
Irina D. Konstantinova 
 
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of 
Sciences, Miklukho-Maklaya st. 16/10, 117997, Moscow 
Natural nucleosides are involved into key biochemical processes such as energy and 
signaling pathways. Adenosine is an intercellular signaling molecule that binds to 
several types of adenosine receptors. The variety of roles and involvement of adenosine 
into enzymatic processes of the cell, as well as its intercellular interaction, allows the 
use of its analogues in the treatment of various diseases. 
The combined chemical-enzymatic approach to the synthesis of new nucleoside 
analogs has become widespread in modern research practice. Libraries of new 
compounds are being actively created. The use of a combination of chemical and 
enzymatic syntheses makes it possible to obtain a wide range of adenosine analogs. 
Methods of chemical synthesis allow to introduce modifications on the purine 
heterocycle. Enzymatic synthesis under mild conditions allows to replace carbohydrate 
residue stable under the conditions of chemical synthesis to a less stable one. 
The reaction of nucleophilic aromatic substitution proceeds easily in the case of 
protected purine nucleosides modified at the C2 position by an electronegative chlorine 
atom. The subsequent removing of acetyl groups by ammonolysis allowed to obtain 
products in high yields. This method was used to obtain series of amino acid, amino 
alcohol, and other derivatives of 2-chloroadenosine. 
The ribosides obtained are substrates for 
E. coli
nucleoside phosphorylases. Using 
the transglycosylation reaction, the corresponding 2'-deoxyribosides were synthesized. 
The new nucleosides showed low toxicity on HepG2 cells and turned out to be