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A Versatile Synthesis of 5′‐Functionalized Nucleosides Through Regioselective Enzymatic Hydrolysis of Their Peracetylated Precursors
Author(s) -
Bavaro Teodora,
Rocchietti Silvia,
Ubiali Daniela,
Filice Marco,
Terreni Marco,
Pregnolato Massimo
Publication year - 2009
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200801096
Subject(s) - chemistry , regioselectivity , pyrimidine , nucleobase , substrate (aquarium) , enzyme , enzymatic hydrolysis , hydrolysis , organic chemistry , combinatorial chemistry , lipase , biocatalysis , nucleoside , purine , catalysis , stereochemistry , biochemistry , reaction mechanism , dna , oceanography , geology
We describe a chemo‐enzymatic synthesis of modified nucleosides through lipase‐catalyzed hydrolysis of their peracetylated precursors. It was found from screening of a large number of substrates that these enzymes' regioselectivities were affected by the sugar and the nucleobase structures. By selecting the best enzyme for each substrate in terms of activity and regioselectivity, we prepared a small library of differently monodeprotected purine and pyrimidine nucleosides useful as intermediates for the synthesis of high‐value nucleosides and mononucleotides. By this approach, the chemo‐enzymatic preparation of doxifluridine ( 14 ) anduridine 5′‐monophosphate (5′‐UMP, 15 ) from peracetylated uridine 1 was carried out. Elimination of many of the processing stages associated with existing methods was achieved, and higher yields and products of increased purity were generated. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)