Synthesis of a Dodecaribonucleotide, GUAUCAAUAAUG, by Use of "Fully" Protected Ribonucleotide Building Blocks

Article abstract of DOI:10.1021/ja00328a042

The fully protected ribonucleotide monomer units (17, 19, 26, and 32) have been synthesized in excellent overall yields from unprotected ribonucleosides.Several carbamoyl groups were tested for protection of the guanosine base moiety.Finally, the diphenylcarbamoyl group was chosen and O⁶-(diphenylcarbamoyl)-N²-propionylguanosine was readily prepared in high yield and converted to the guanosine units 12 and 17.The uridine unit 19 was prepared by the acylation of the previous unit 18 with anisoyl chloride in the presence of i-Pr2EtN.In the case of the adenosine and cytidine units (26 and 32) , the regioselective 2'-O-tetrahydropyranylation was involved in their syntheses.These "perfectly" protected monomer units have succesfully been utilized in the synthesis of GUAUCAAUAAUG, a modified 5'-terminal structure, of brome mosic virus (BMV) mRNA no. 4 filament.The dodecamer chain was elongated by fragment condensation from the 3'-5' direction.The yields of the oligomer blocks have proved to be dramatically high because no side reactions occurred during the condensation reactions.Indeed, the final coupling to give the target 12-mer was achieved in 91percent yield.The deprotection of the fully protected in the usual manner gave GUAUCAAUAAUG in ca. 30percent yield.