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Title: Diastereoselective Synthesis of cycloSaligenyl-Nucleosyl-Phosphotriesters
Authors: Rios Morales, Edwuin H ×
Balzarini, Jan
Meier, Chris #
Issue Date: Feb-2011
Publisher: VCH Verlagsgesellschaft
Series Title: Chemistry - a European Journal vol:17 issue:5 pages:1649-59
Article number: 10.1002/chem.201002657
Abstract: A diastereoselective synthesis of cycloSal-phosphotriesters (cycloSal=cycloSaligenyl) based on chiral auxiliaries has been developed that allows the synthesis of single diastereomers of the cycloSal-pronucleotides. In previously described synthesis routes, the cycloSal-compounds were always obtained as 1:1 diastereomeric mixtures that could be separated in only rare cases. However, it was shown that the diastereomers have different antiviral activity, toxicity, and hydrolysis stabilities. Here, first a chiral thiazoline derivative was used to prepare nonsubstituted and 5-methyl-cycloSal-phosphotriesters in 48 and ≥95 % de (de=diastereomeric excess). However, this approach failed to give the important group of 3-substituted cycloSal-nucleotides. Therefore, two other chiral groups were discovered that allowed the synthesis of (R(P) )- and (S(P) )-3-methyl-cycloSal-phosphotriesters as well. The antiviral activity was found to be five- to 20-fold different between the two individual diastereomers, which proved the importance of this approach.
URI: 
ISSN: 0947-6539
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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