Partial protection of carbohydrate derivatives. Part 3. Regioselective 2′-O-deacylation of fully acylated purine and pyrimidine ribonucleosides with hydrazine hydrate

Abstract

In 1 : 4 (v/v) glacial acetic acid–pyridine, partial O-deacylation of fully acylated purine and pyrimidine ribonucleosides upon hydrazinolysis was found to be induced regioselectively in respect to the three ester functions at the 2′-position to give the corresponding 2′-OH derivatives in good yields; e.g. 3′, 5′-di-O-benzoyladenosine (70% yield), N², 3′, 5′-tribenzoylguanosine (63% yield), 3′, 5′-di-O-benzoylinosine (52% yield), N²-benzoyl-3′, 5′-di-O-acetylguanosine (42% yield), and 3′, 5′-di-O-benzoyluridine (39% yield) were isolated. Moreover, 5′-O-acylribonucleosides were prepared in quantitative yields by use of an excess of hydrazine hydrate in 1 : 1 (v/v) chloroformmethanol and in pyridine. Hydrazinolysis of 3′, 5′-di-O-acetyl-2′-deoxyribonucleosides in pyridine was found to give both 5′, and 3′-O-acetyl-2′-deoxyribonucleosides in comparable amounts (80–90% total yields).

Furthermore, hydrazinolysis of N⁶, 2′, 5′-triacetyl-3′-O-methyladenosine and N⁶, 3′, 5′-triacetyl-2′-O-methyladenosine demonstrated that the 2′-O-acetyl group is far more labile toward the nucleophile than the 3′-O-acetyl group.

The possible factors involved in the regioselectivity of hydrazinolysis are discussed.