3-deoxy-3,3-difluoro-D-arabinofuranose: first stereoselective synthesis and application in preparation of gem-difluorinated sugar nucleosides.
The design and synthesis of gem-difluorinated sugar nucleosides were described. The key intermediate, 3-deoxy-3,3-difluoro-d-arabinofuranose 9, was first stereoselectively prepared from the chiral gem-difluorohomoallyl alcohol 12. The kinetic formation of single anti-14 in the benzylation of 12 could be accomplished by controlling the amount of sodium hydride used. The dihydroxylation of 14 (a mixture of anti and syn isomers) followed by deprotection and oxidation stereoselectively afforded furanose 9 with the arabino configuration at the C2 position. N(1)-(3-Deoxy-3,3-difluoro-beta-D-arabinofuranosyl)cytosine 6 was prepared from 9 by the glycosylation reaction. 4'-Thiofuranose 25 was easily synthesized from 9. The oxidation of 25 followed by the condensation with silylated N(4)-benzoylcytosine (Pummerer reaction) failed to give our desired protected nucleoside l-3'-deoxy-3',3'-difluoro- 4'-thiocytidine 27', but the regioisomer 27 was obtained. The regiochemistry of the Pummerer reaction was determined by the kinetic acidity of the alpha-proton of 4'-thiofuranose 25.
Zhang
Xingang
X
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, 354 Fenglin Lu, Shanghai 200032, China.
Xia
Hairong
H
Dong
XiCheng
X
Jin
Jing
J
Meng
Wei-Dong
WD
Qing
Feng-Ling
FL
D001089:Arabinose / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D010084:Oxidation-Reduction; D013237:Stereoisomerism
C482965:3-deoxy-3,3-difluoro-D-arabinofuranose; D009705:Nucleosides; D001089:Arabinose