A Unified Strategy to Fluorinated Nucleoside Analogues Via an Electrophilic Manifold
Andrew J Neel1, Ben W H Turnbull1, William P Carson1
1Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Abstract:
Herein, we present a strategy for the preparation of 3'-fluorinated nucleoside analogues via the aminocatalytic, electrophilic fluorination of readily accessible and bench-stable 2'-ketonucleosides. Initially developed to facilitate the manufacture of 3'-fluoroguanosine (3'-FG)─a substructure of anticancer therapeutic MK-1454─this strategy has been extended to the synthesis of a variety of 3'-fluoronucleosides. Finally, we demonstrate the utility of the 2'-ketonucleoside synthon as a platform for further diversification and suggest that this methodology should be broadly applicable to the discovery of novel nucleoside analogues.
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