The synthesis of oligoribonucleotides—VIII: The preparation of ribonucleoside 2′,5′-bisketals

Abstract

The conversion of N 4-benzoylcytidine, N 4-anisoylcytidine, N 2-benzoylguanosine and inosine into their 3′-acetates, and N 6,N 6-dimethyladenosine into its 3′-benzoate by the orthoester exchange method, are described. All these 3′-O-acyl derivatives (IX) were obtained crystalline and in good or satisfactory yields. 2′-O-Acetyl-N 4-anisoylcytidine (XIIIb) and 2′-O-benzoyl-N 6,N 6-dimethyladenosine (XVII) were also obtained crystalline. The above 3′-O-acyl derivatives, and also 3′-O-acetyl-uridine and -adenosine, were treated with 4-methoxy-5,6-dihydro-2 H-pyran (X) in the presence of acid to give the corresponding 3′-O-acyl ribonucleoside 2′,5′-bisketals (XI) in good yields. Treatment of the latter with base gave the desired ribonucleoside 2′,5′-bisketals (V). Some of the bisketal esters (XI) and most of the bisketals (V) were isolated as pure crystalline solids. Treatment of the uridine 2′,5′-bisketal (V; B = uracil-1) with aqueous acid under controlled conditions revealed that its 5′-ketal function was ca. twice as labile to acidic hydrolysis as its 2′-ketal function.