Difluorophosphonylated Allylic Ether Moiety as a 2'-Modification of RNA-Type Molecules: Synthesis, Thermal, and
Emmanuel Pfund1, Christelle Dupouy2, Sonia Rouanet2
1Normandie Université, Laboratoire de Chimie Moléculaire et Thioorganique , UMR 6507, ENSICAEN, UNICAEN, CNRS, 6 Bd du Maréchal Juin , 14050 Caen , France.
Abstract:
The first synthesis of oligonucleotides incorporating URF, a uridine modified with a difluorophosphonylated allylic ether onto the 2'-position, is described. Fluorinated homouridylates and miR-342-3p analogues are efficiently prepared. UV-melting experiments and enzymatic degradation studies indicate this new series of fluorinated oligonucleotides exhibit good and thermal metabolic stability as well as an increased lipophilicity. Comparison with oligonucleotides containing 2'- O-allyluridine instead of URF reveals improvement of these chemical properties is related to the presence of the difluoromethylphosphonate group.
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