Practical Synthesis of Fludarabine and Nelarabine

Abstract

A new practical synthesis strategy has been developed to access­ the β-d-arabinofuranosyl purine nucleosides fludarabine and nelarabine. In our approach, an ortho-alkyne benzoyl ester is transiently introduced as a neighbouring-participation group in Vorbrüggen glycosylation to afford the corresponding β-nucleoside exclusively. The latter was further removed efficiently by using freshly prepared Ph₃PAuOTFA to give the corresponding 2′-OH nucleosides without transesterification. After reversion of the configuration of 2′-OH and deprotection, fludarabine and nelarabine were obtained in high yield and purity.

Key words

fludarabine - nelarabine - gold(I) catalysis - total synthesis - ortho-alkyne benzoyl ester - β-d-arabinofuranosyl purine nucleosides - Vorbrüggen glycosylation

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