Action of acid on oligoribonucleotide phosphotriester intermediates. Effect of released vicinal hydroxy functions

Abstract

When 2′-O-methoxytetrahydropyranyl-5′-O-(9-phenylxanthen-9-yl) uridylyl-(3′←5′)-(2′ ,3′-di-O-acetyluridine) 2-chlorophenyl ester (9) is treated with zinc bromide in dichloromethane-propan-2-ol (85:15 v/v) at room temperature, under stringently anhydrous conditions, the corresponding 5′-unblocked dinucleoside phosphate (10) is obtained in 86% isolated yield; however, when no special precautions are taken to exclude moisture, (10) is obtained in only 72% yield. The removal of the 5′-O-(9-phenylxanthen-9-yl) protecting group from (10) with a protic acid (phenyl dihydrogen phosphate) appears to be much less selective and efficient. 80% Acetic acid promoted removal of the methoxytetrahydropyranyl protecting group from the isomeric fully-protected uridylyl-(3′←5′)- and uridylyl-(2′←5′)-uridine derivatives [(11) and (21c), respectively] leads to virtually identical mixtures (Figures 1a and 1b respectively] of the partially-protected dinucleoside phosphates [(14) and (15)], 2′ ,3′-di-O-acetyluridine (8), 5′-O-acetyluridine 2′ ,3′-cyclic phosphate (16), and 5′-O-acetyluridine 2′(3′)-phosphates [(18) and (17)].