Organizing co mmittee

SYNTHESIS OF NEW BENZIMIDAZOLE NUCLEOSIDES 
 
I.A. Aleksakhina
1
, A.L. Kayushin 
2
, A.O. Arnautova 
2 
 
1
MIREA – Russian Technological University, 86 Vernadsky Avenue, Moscow, 
119571, Russia 
2
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAS, Miklukho-
Maklaya 16/10, 117997 GSP, B-437 Moscow, Russia 
The development of benzimidazole nucleosides as antiviral drugs is a rapidly 
evolving field. Researchers are ongoing to improve their potency, specificity, and safety 
profile. Various modifications have been made to the structure of benzimidazole 
nucleosides, for instance, modifications of benzimidazole cycle or ribose residue. 
In this study we synthesized a number of benzimidazole ribosides. 
An effective biotechnological method for synthesis of modified benzimidazole 
nucleosides has been developed. 
Syntheses of benzimidazole and 4,6-difluoro-5-O-methylbenzimidazole 3'-
deoxyribosides were optimized as follows:
 
• The amount of purine nucleoside phosphorylase (PNP) (2800 units for synthesis 
with Benz, 2100 units for synthesis with Sk-473) 
• Substrate ratio (Benz:3'dIno and Sk-473:3'dIno 2:6 and 1:7, respectively); 
After optimizing the conditions, preparative syntheses of benzimidazole nucleosides 
were performed. Structures of target compounds were confirmed by NMR and mass 
spectrometry. 
Yields of benzimidazole and Sk-473 3'-deoxyribosides were 26% and 70% 
correspondingly. 
Studies of antiviral activity and cytotoxic properties of nucleosides obtained have 
shown that benzimidazole and Sk-473 3'-deoxyribosides developed significant 
antiherpetic activity. Right now further investigations are performed. 
The study was supported by RSF grant (Project No. 21-13-00429). 
.
NH
N
N
O
N
O
OH
H
H
H
HO
N
H
N
KH
2
PO
4
PNP
N
N
O
OH
H
H
H
HO
NH
N
N
O
N
H
+
+
.
Y
Z
Y
Y
Z
Y
3'-deoxyinosine
Y, Z=H - Benzimidazole (Benz)
Y=F, Z=OMe - 4,6-difluoro-5-o-methyl-
benzimidazole (Sk-473)
Y, Z=H - Benzimidazole 3'-deoxyriboside
Y=F, Z=OMe - 4,6-difluoro-5-o-methyl-
benzimidazole 3'-deoxyriboside
Hypoxanthine

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Poster presentation 
59