Diversely C8-functionalized adenine nucleosides via their underexplored carboxaldehydes
Hari K Akula1, Suyeal Bae1, Padmanava Pradhan1
1Department of Chemistry and Biochemistry, The City College of New York, 160 Convent Avenue, New York, NY 10031, USA. bzajc@ccny.cuny.edu.
Abstract:
The potentially versatile N-unprotected 8-formyl derivatives of adenosine and 2'-deoxyadenosine are highly underexploited for C8 modifications of these nucleosides. Only in situ formation of 8-formyladenosine is known and a single application of an N-benzoyl derivative has been reported. On the other hand, 8-formyl-2'-deoxyadenosine and its applications remain unknown. Herein, we report straightforward, scalable syntheses of both N-unprotected 8-formyladenine nucleoside derivatives, and demonstrate broad diversification at the C8 position by hydroxymethylation, azidation, CuAAC ligation, reductive amination, as well as olefination and fluoroolefination with modified Julia and a Horner-Wadsworth-Emmons reagents.
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