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

摘要

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 adenosine, or with O6-protected guanosine and N3,5′-Oprotected 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.