Microwave-Assisted Phosphitylation of DNA and RNA Nucleosides and Their Analogs

Abstract

Microwave-assisted chemical phosphitylation of novel nucleoside analogs containing a ribulose sugar unit was successful with yields ranging from 50% to 79% using 2-cyanoethyl-N,N-diisopropyl chlorophosphoramidite as the phosphitylating reagent. The resultant phosphoramidite products remained intact, with no signs of degradation over extended reaction times (up to 60 min) at an elevated temperature (65°C). When the same microwave-mediated phosphitylating protocols were applied to canonical DNA and RNA nucleoside monomers as substrates, using either 2-cyanoethyl-N,N,-diisopropyl chlorophosphoramidite or 2-cyanoethyl-N,N,N′,N′-tetraisopropyl phosphane with an activator, 40% to 90% yields of DNA and RNA phosphoramidites were obtained within 10 to 15 min. These results demonstrate that microwave-assisted phosphitylation is an efficient alternative to standard phosphitylating conditions that can be expanded and refined to include a variety of substrates. © 2015 by John Wiley & Sons, Inc.