Regio- and stereoselective syntheses of L-pentose derivatives from L-arabinose

Novel L-arabinose, L-ribose, 2-deoxy-L-ribose and 2-fluoro-2-deoxy-L-arabinose derivatives were synthesized from readily available L-arabinose. Different synthetic routes to methyl 3,5-di-O-acylated-L-arabino(ribo)furanosides as valued intermediates for the preparation of C-2 functionalized L-pentoses were investigated via regioselective transformations of 1,2-di-O-acetyl-3,5-di-O-pivaloyl-L-arabinofuranose, and selective acylation of methyl L-arabinofuranoside with 4-chlorobenzoyl or pivaloyl chloride. Short three-five-step syntheses of methyl 2-deoxy-alpha-L-ribofuranoside, its 3,5-di-O-acyl derivatives, valuable precursors for preparation of antiviral 2'-deoxy-L-nucleosides, were accomplished via simple and efficient reduction of methyl 2-O-mesyl-L-arabinofuranoside with L-Selectride or tandem reaction involving a complex hydride 2-deoxygenation/acylation of intermediate 2-deoxysugar. A new synthesis of 2'-deoxy-2'-fluoro-beta-L-arabinofuranosyl thymine (L-FMAU) was performed using a mild fluorination of protected L-ribofuranoside and a novel sequence of conversions for the preparation of 2-deoxy-2-fluoro-L-arabinofuranoside derivatives. (C) 2018 Elsevier Ltd. All rights reserved.