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Synthesis of 3′,5′‐Cyclic Phosphate and Thiophosphate Esters of 2′‐ C ‐Methyl Ribonucleosides
Author(s) -
Leisvuori Anna,
Ahmed Zafar,
Ora Mikko,
Beigelman Leonid,
Blatt Lawrence,
Lönnberg Harri
Publication year - 2012
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.201200099
Subject(s) - chemistry , thiophosphate , phosphate , stereochemistry , nucleoside , nucleotide , biochemistry , organic chemistry , gene
2′‐ C ‐Methylnucleosides are known to exhibit antiviral activity against Hepatitis C virus. Since the inhibitory activity depends on their intracellular conversion to 5′‐triphosphates, dosing as appropriately protected 5′‐phosphates or 5′‐phosphorothioates appears attractive. For this purpose, four potential pro‐drugs of 2′‐ C ‐methylguanosine, i.e. , 3′,5′‐cyclic phosphorothioate of 2′‐ C ‐methylguanosine and 2′‐ C , O 6 ‐dimethylguanosine, 1 and 2 , respectively, the S ‐[(pivaloyloxy)methyl] ester of 2′‐ C , O 6 ‐dimethylguanosine 3′,5′‐cyclic phosphorothioate and the O ‐methyl ester of 2′‐ C , O 6 ‐dimethylguanosine 3′,5′‐cyclic phosphate, 3 and 4 , respectively, have been prepared.