RNA-SYNTHESIS USING A UNIVERSAL, BASE-STABLE ALLYL LINKER

The application of a universal allyl linker, 9-O-(4,4'-dimethoxytrityl )-10-undecenoic acid, to the solid phase synthesis of RNA molecules is described, Use of this linker simplifies significantly the isolation and purification steps in RNA synthesis, The linker is universal in th at it does not contain a nucleoside, The 3' terminal nucleoside is ins tead attached to the support in the first coupling step, The resultant RNA fragment is then obtained as the 3'-phosphate. The linker is base -stable, and thus all reagents used during deprotection can simply be washed away, leaving the RNA attached, Further, tritylated short fragm ents resulting from chain cleavage for any reason are also washed away before separation from the support, This linker is compatible with an y current synthetic methodology and any amino functionalized support, Of course, silica supports would not be compatible with fluoride reage nts, It could also be used to advantage for other applications, Becaus e it is cleaved under conditions orthogonal to those used during many common reactions, the range of postsynthetic manipulations that can be carried out without cleavage from the support is extended significant ly.