Oligoribonucleotide Synthesis. II. Preparation of 2′-O-tetrahydropyranyl Derivatives of Adenosine and Cytidine Necessary for Insertion in Stepwise Synthesis

Abstract

The syntheses of N6-benzoyl-2′-O-tetrahydropyranyladenosine (2) and N4-benzoyl-2′-O-tetrahydropyranylcytidine (11) and their corresponding 5′-O-p-methoxytrityl derivatives, 3 and 12 respectively, are described. Compounds 2, 3, 11, and 12 are the protected derivatives of adenosine and cytidine required for insertion into a new oligoribonucleotide synthesis. Compound 2 was prepared from the known 2′-O-tetrahydropyranyladenosine by perbenzoylation followed by de-O-benzoylation. Compound 11 is prepared from cytidine by the following sequence: orthoacetate protection of the 2′- and 3′-hydroxyls; benzoylation of the 5′- and N4-positions; orthoacetate ring opening provided a mixture of the 2′- and 3′-monoacetates from which the major, 3′-O-acetyl-N4,5′-O-dibenzoylcytidine (7) was isolated; dihydropyran treatment on the 2′-hydroxyl of 7 and subsequent selective deacylation studies were carried out. Specific de-O-acylation gave 11.