Optimized synthesis of LNA uracil nucleosides

Abstract

A short, very high yielding, and practical synthesis of LNA uracil diol 6 has been developed from the easily accessible glycosyl donor 1. The concluding O3′-debenzylation of 5 resulted in significant reduction of the uracil moiety with many typical debenzylation conditions, while catalytic transfer hydrogenation using Pd(OH)2/C and formic acid largely suppressed this undesired side reaction. Facile access to 6 will allow full exploration of RNA-based LNA-technology applications, including polymerase-catalyzed synthesis of LNA-modified RNA-strands. © 2008 Elsevier Ltd. All rights reserved.