Synthesis of 2-fluoro-substituted and 2,6-modified purine 2′,3′-dideoxy-2′,3′-difluoro-D-arabinofuranosyl nucleosides from D-xylose

TETRAHEDRON

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Article

Sivets, Grigorii G.¹  Amblard, Franck²  Schinazi, Raymond F.² 

[1] Natl Acad Sci Belarus, Inst Bioorgan Chem, 5-2 Acad Kuprevicha, Minsk 220141, BELARUS

[2] Emory Univ, Ctr AIDS Res, Dept Pediat, Lab Biochem Pharmacol,Sch Med, Atlanta, GA 30322 USA

关键词: D-xylose;    Regioselective benzoylation;    Fluorination;    Fluorodeoxy sugars;    Glycosylation;    Fluoronucleosides;   

DOI  :  10.1016/j.tet.2019.02.027

来源: Elsevier

【 摘 要 】

A series of novel purine-modified 2',3'-dideoxy-2',3'-difluro-D-arabinonucleosides, including fluorinated analogs of fludarabine and nelarabine, have been prepared via anion glycosylation reactions of salts of 2-fluoropurine derivatives with the glycosyl bromide. A short and efficient synthetic route to the carbohydrate precursor 5-O-benzoyl-2,3-difluoro-alpha-D-arabinofuranosyl bromide was developed in five steps from D-xylose. Improved synthesis of methyl 5-O-benzoyl-2,3-difluoro-alpha-D-arabinofuranoside based upon the study of diethylaminosulfur trifluoride (DAST)-reactions with 5-O-protected methyl D-xylosides was explored using mild reaction conditions on the key step. New peculiarities for selective fluorinations of 5-O-benzoylated alpha- and beta-D-pentofuranosides with DAST leading to the formation of mono and difluoro-furanoside derivatives are reported. (C) 2019 Elsevier Ltd. All rights reserved.

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