A simple procedure for the preparation of protected 2'-0- methyl or 2'-O-ethyl ribonucleoside-3'-O-phosphoramidites

Protected 2'-O-methyl and 2'-O-ethyl ribonucleoside-3'-O-phosphoramidites were prepared via alkylation of the ribonucleosides at an early stage in the synthesis. Utilizing a strategy of minimal protection, the alkylation was performed with unprotected cytidine and adeno-sine, or with O6-protected guanosine and N3,5'-O-protected uridine using methyl or ethyl iodide and sodium hydride. In subsequent steps, the introduction of standard protective groups for oligonucleotide synthesis and the concomitant separation from 3-0-alkylated isomers was accomplished. A modification of the phosphitylation procedure permitted facile isolation of the desired phosphoramidites which show high coupling efficiencies in oligomer assembly