Nucleosides. Part LXIII. Acetals as new 2′‐O‐protecting functions for the synthesis of oligoribonucleotides: Synthesis of uridine building blocks and evaluation of their relative acid stability

Abstract

AbstractA broad variety of new acyclic vinyl ethers (see 6–41) have been synthesized via the vinyl‐interchange reaction of ethyl vinyl ether at room temperature using mercury(II) trifluoroacetate as a highly efficient catalyst. The appropriate vinyl ethers were reacted under acidic conditions with 3′,5′‐O‐silyl‐protected uridine 42 to the corresponding 2′‐O‐(1‐alkoxyethyl) derivatives 43–83 which gave, on desilylation of F− ions, in high yields the uridine‐2′‐O‐acetal derivatives 84–124. The relative stabilities of the newly synthesized compounds under acidic and basic conditions were determined using TLC and HPLC techniques. Protected protecting groups offer the best properties for oligoribonucleotide syntheses. Interestingly, the very acid‐stable acetals of the β‐substituted ethyl‐type 118–121 and 123 can be cleaved by a β‐elimination process providing a series of base‐labile acetals of potential synthetic value.