The synthesis of oligoribonucleotides. Part IX. Preparation of ribonucleoside 2′-acetal 5′-esters

Abstract

The preparation of trimethyl methoxyorthoacetate (XVIII) and its acid-catalysed reactions with uridine, cytidine, and adenosine to give satisfactory yields of the corresponding 2′,3′-cyclic methoxyorthoacetates (XIX) are described. The preparations of crystalline 4-N-benzoyl-3′-O-formyl-5′-O-methoxyacetyladenosine (XIV), 5′-O-benzoyl-3′-O-methoxyacetyluridine (XX), 4-N,5′-O-diacetyl- and 4-N,5′-O-dianisoyl-3′-O-methoxyacetylcytidines (XXII; R = Me or p-MeO·C₆H₄, respectively), and 6-N,5′-O-dianisoyl-2′-O-methoxyacetyladenosine (XXIV; R =p-MeO·C₆H₄) are described.

The acid-catalysed reaction between 5,6-dihydro-4-methoxy-2H-pyran and 2-N,5′-O-dibenzoyl-3′-O-formylguanosine (XI), followed by selective deformylation, gave 2-N,5′-O-dibenzoyl-2′-O-methoxytetrahydropyranylguanosine (XII). In the same way (i.e. acetalization followed by selective deformylation or demethoxyacetylation), compounds (XIV), (XX), and (XXII)(R =p-MeO·C₆H₄) were converted into the corresponding crystalline 2′-O-methoxytetrahydropyranyl-5′-O-acyl ribonucleoside derivatives [(XV), (XXI), and (XXIII)(R =p-MeO·C₆H₄), respectively] in satisfactory yields. 2′-O-Methoxytetrahydropyranyluridine (XXV) has been found to undergo selective p-chlorophenoxyacetylation on its 5′-hydroxy-group.