Purines. XI. The Synthesis of N-Alkoxyadenosines and Their 2', 3'-O-Isopropylidene Derivatives

Abstract

Alkylation of adenosine 1-oxide (I) and its 2', 3'-O-isopropylidene derivative (V) with alkyl halides in N, N-dimethylacetamide furnished the corresponding 1-alkoxy derivatives (IIa-f). The free bases, obtained from IIa-f, readily underwent rearrangement to give the isomeric N6-alkoxy derivatives (IVa-f) when heated in water. Treatment of 1-benzyloxyadenosine perchlorate (IIc : X=ClO4) with water at pH 9.5 and 39-41°for 4 hr afforded the ring-opened intermediate (IIIc)(79% yield), which was recyclized in hot water (pH 7) to IVc. In alternative synthesis of IVa, b, c, condensation of 6-chloro-6-β-D-ribofuranosylpurine (VIa) with the appropriate alkoxyamines proceeded smoothly. Removal of the isopropylidene group from IVe under acid conditions or exchange amination of adenosine with ethoxyamine at pH 5 also yielded N-ethoxyadenosine (IVb).