SYNTHESIS OF OLIGORIBONUCLEOTIDES .4. PREPARATION OF DINUCLEOSIDE PHOSPHATES FROM 2',5'-PROTECTED RIBONUCLEOSIDE DERIVATIVES

The preparation of 2′-O-tetrahydropyranyl-uridine and -adenosine is described. Both diastereoisomers of each derivative have been isolated in a pure crystalline state. The high-melting (more laevorotatory) diastereoisomer derived form each nucleoside has been converted to its 5′-O-pivaloyl derivative. Both diastereoisomers of 2′-O-tetrahydropyranyl-5′-O-pivaloyluridine have been independently prepared from 3′-O-acetyl-′-O-pivaloyluridine, condensed with 2′,3′-O-methoxymethylideneuridine 5′-phosphate, and thereby converted into uridylyl-(3′ → 5′)-uridine in good yield. The 2′-O-tetrahydropyranyl protecting group may be removed by acidic hydrolysis (with 0-01N HCI) under very mild conditions which lead to a negligible amount of isomerization (by phosphoryl migration) and degradation of the dinucleoside phosphate. Each of the dinucleoside phosphate: adenylyl -(3′ → 5′)-uridine, uridylyl-(3′ → 5′)-uridine, uridylyl-(3′ → 5′)-adenosine, uridylyl-(3′ → 5′)-cytidine and adenylyl-(3′ → 5′)-cytidine has also been prepared in the same way from the appropriate 2′-O-tetrahydropyranyl-5′-O-pivaloyl nucleoside. © 1968.