Partial protection of carbohydrate derivatives. Part 4. Regioselective 2′-O-deacylation of fully acylated purine and pyrimidine ribonucleosides with hydroxylaminium acetate

Abstract

Like hydrazine hydrate, hydroxylamine was found to be useful for the regioselective 2′-O-deacylation of fully acylated purine and pyrimidine ribonucleosides as its salt with acetic acid; the partial O-deacylation reactions (which were not accompanied by undesirable discolouration as happens with hydrazine hydrate) gave the corresponding di-O-acylribonucleosides in superior yields; e.g. 2′,3′-di-O-benzoyladenosine (74% yield), 3′,5′-(64% yield) and 2′,5′-di-O-benzoyl-N⁶-benzyladenosine (63% yield on performing the reaction in ethanol), N²,3′,5′-tri-O-benzoylguanosine (66% yield), N²,2′.5′-tri-isobutyrylguanosine (48% yield), and 3′,5′-di-O-benzoyluridine (61% yield) were obtained using hydroxylaminium acetate in pyridine. Treatment of fully acetylated ribonucleosides with an excess of hydroxylaminium acetate gave the corresponding 5′-O-acetylribonucleosides in quantitative yields.

The excellent regioselectivityobserved inthe present partial O-decyclation was confirmed onthe basis of chromatographic separation; the mixtures of di-O-acylribonucleosides, which had already been equilibrated in pyridine, were re-equilibrated on the silica gel during separation, e.g, a 70 : 30 mixture of 3′,5′- and 2′,5′-di-O-benzoyladenosine was completely converted into the former based on ¹H n.m.r. spectroscopy. The acetates of 9-β-D-xylo- and -arabino-furanosyladenine were also found to give predominantly the corresponding 3′,5′-diacetates on hydroxylaminolysis.