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Alternative Syntheses of (S)‑cEt-BNA: A Key Constrained Nucleoside Component of Bioactive Antisense Gapmer Sequences

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journal contribution
posted on 05.12.2014, 00:00 by Juan C. Salinas, Michael T. Migawa, Bradley L. Merner, Stephen Hanessian
Approaches to the synthesis of the constrained 5-methyluracil nucleoside (S)-cEt-BNA, a key “gapmer” unit in a number of biologically relevant antisense oligonucleotides, are described using 5-methyluridine as starting material. In the shorter synthesis, a nine-step linear sequence afforded a O-protected (S)-cEt-BNA consisting of a [2.2.1]­dioxabicycloheptane core in 7% overall yield. A competing reaction in an intramolecular cyclization of a tosylate led to a bicyclic oxetane.