Organizing co mmittee

SYNTHESIS OF 2-FLUOROCORDYCEPINE 
 
Alexandra O. Arnautova, Alexey L. Kayushin, Konstantin V. Antonov, Irina D. 
Konstantinova 
 
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of 
Sciences, Miklukho-Maklaya 16/10, 117997 GSP-7, Moscow B-437, Russia 
2-Fluorocordycepine (2-fluoro-3’-deoxyadenosine) is a potential effective antitumor 
and antiviral drug. We obtained 2-fluorocordycepin (2-F-Cord) (
2
) in two ways: by 
chemical synthesis and by enzymatic way using two different sources of 3-deoxyribose. 
Method 1. The chemical synthesis was performed in 3 stages. In the first step, the 
initial 2-fluoroadenosine (2-F-Ado) (
1
) was treated with α-acetoxyisobutyryl bromide to 
form two protected bromine derivatives. Resulting mixture was dehalogenated using 
H
2
/Pd, resulting in a mixture of protected 3'-deoxynucleosides. The protection groups 
were removed with aqueous methanol ammonia solution to form desired compound 
2
and 2-aminocordycepine 
3
in ratio 85:15 respectively. 2-F-Cord was isolated by 
reversed-phase chromatography with 28% yield. 
Method 2a. The enzymatic synthesis was performed using 3'-deoxyinosine (
4
) and 
nucleoside 
1
in presence of recombinant 
E. coli
purine nucleoside phosphorylase (PNP). 
Conditions: ratio of substrates (
4
):(
1
) - 1.5:1.0, 2 mM potassium-phosphate buffer (pH 
7.0), PNP - 2100 units, 50 ⁰С, the reaction time - 16 days. 2-F-Cord was isolated with 
60% yield. 
Method 2b. Lithium salt of 3-deoxyribose phosphate (
5
) and compound 
1 
were used 
in the transglycosylation reaction as substrates. Conditions: ratio of substrates (