Organizing co mmittee

C
HEMO
-
ENZYMATIC SYNTHESIS OF NEW RIBAVIRIN ANALOGS
 
 
Olga S. Smirnova, Irina D. Konstantinova 
 
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of 
Sciences, Miklukho-Maklaya St. 16/10, 117997, Moscow B-437, Russian Federation. 
 
Ribavirin, 
1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide, 
is 
a 
modified 
nucleoside with broad spectrum antiviral activity. The disadvantage of ribavirin is its 
cytotoxicity and teratogenicity. For this reason, the search for new safe drugs does not 
lose its relevance. The biotechnological method for the synthesis of new ribavirin 
analogs by the transglycosylation reaction has a number of advantages over multi-stage 
chemical synthesis: high efficiency, regio- and stereoselectivity. Testing of new bases of 
1,2,4-triazole as substrates of 
E. coli
purine nucleoside phosphorylase (PNP) helps to 
reveal the structural features of substrates that determine the possibility of carrying out 
the reaction of synthesis of modified nucleosides in the active center of the enzyme. 
E. 
coli
PNP is able to synthesize ribonucleosides and 2'-deoxyribonucleosides having 
structurally different alkyl(aryl)oxymethyl substituents at the C5 position of 1,2,4-
triazole-3-carboxamide. 
A 
number 
of 
5-alkyl/aryloxymethyl-1,2,4-triazole-3-
carboxamide nucleosides have been synthesized. It has been established that N-cyclic 
(C-5, C-6, C-7) aliphatic 1,2,4-triazolecarboxamides are substrates with a degree of 
conversion to the corresponding nucleosides up to 99%.
After optimizing the conditions for carrying out enzymatic reactions a number of 
ribo- and 2-deoxyribonucleosides of N-substituted 1,2,4-triazolecarboxamides were 
synthesized (yields up to 90%). Currently, the Gamaleya National Research Center for 
Epidemiology and Microbiology studies the antiviral activity of the synthesized 
compounds on models of herpes simplex viruses and influenza type A virus. 
This research was funded by the Russian Science Foundation (Project No. 21-13-
00429) 
Urd/dUrd
Urd/dUrd
HN
N
N
O
NH
2
RO
E. coli 
PNP, UP
N
N
N
O
NH
2
RO
O
R
1
HO
HO
HN
N
N
O
NH
E. coli 
PNP, UP
O
R
1
HO
HO
N
N
N
O
N
H
+
R
1
=OH, H
R=H, Me, Et, (CH
2
)
2
OMe, 
n-Bu, CH
2
-Ph
R
1
=OH, H; n= 1, 2, 3
UP - uridine nucleoside phosphorylase
+
( )
n
( )
n

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Poster presentation 
47