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Published on: August 19, 2012
An enantioselective and modular platform for C4'-modified nucleoside analogue synthesis enabled by intramolecular
Thirupathi Nuligonda1, Gautam Kumar1, Jason W Wang1
1Department of Chemistry, University of Alberta, Edmonton, AB, Canada.
None:
C4'-modified nucleoside analogues continue to attract global attention for their use in antiviral drug development and oligonucleotide-based therapeutics. However, current approaches to C4'-modified nucleoside analogues still involve lengthy (9-16 steps), non-modular routes that are unamenable to library synthesis. Towards addressing the challenges associated with their syntheses, we report a modular 5-step process to a diverse collection of C4'-modified nucleoside analogues through a sequence of intramolecular trans-acetalizations of readily assembled polyhydroxylated frameworks. Overall, the 2-3 fold reduction in step-count compares favorably to even recently reported biocatalytic approaches and should ultimately enable new opportunities in drug design around this popular chemotype.
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