Stereoselective synthesis of 2-deoxy-2-fluoroarabinofuranosyl-alpha-1-phosphate and its application to the synthesis of 2'-deoxy-2'-fluoroarabinofuranosyl purine nucleosides by a chemo-enzymatic method.
Stereoselective introduction of a phosphate moiety into 2-deoxy-2-fluoroarabinofuranose derivatives at the anomeric position was investigated by two methods. One involved a stereoselective hydrolysis of 1-bromo-derivative, and the consecutive phosphorylation of 2-deoxy-2-fluoro-alpha-D-arabinofuranose via a phosphoramidite derivative. The other method involved stereoselective alpha-phosphorylation of the 1-bromo-derivative at the 1-position. The resulting alpha-1-phosphate was utilized to prepare 2'-deoxy-2'-fluoroarabinofuranosyl purine nucleosides by an enzymatic glycosylation reaction. This chemo-enzymatic method will be applicable to the synthesis of some 2'F-araNs, and three important 2'F-araNs were actually obtained in 30-40% yields from 1,3,5-tri-O-benzoyl-2-deoxy-2-fluoro-alpha-D-arabinose with high purity.
Yamada
Kohei
K
Biochemicals Division, Yamasa Corporation, Choshi, Chiba, Japan. k_yamada@yamasa.com
Matsumoto
Noritake
N
Hayakawa
Hiroyuki
H
D001087:Arabinonucleosides / Q000737:chemistry*; D002384:Catalysis; D005461:Fluorine / Q000737:chemistry*; D015394:Molecular Structure; D010766:Phosphorylation; D011684:Purine Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D001087:Arabinonucleosides; D011684:Purine Nucleosides; D005461:Fluorine