Practical synthesis of 2'-deoxy-2'-fluoroarabinofuranosyl purine nucleosides by chemo-enzymatic method.
Stereoselective introduction of a phosphate group into 2-fluorinated sugar (4) at the 1-position was developed by us for the first time. The resulting alpha-1-phosphate (1) was utilized to prepare 2'-deoxy-2'-fluoroarabinofuranosyl purine nucleosides (2), which were the key starting materials for the preparation of the 2'F-ANA-antisense molecule, by enzymatic glycosidation reaction. Next, we tried to apply this method as a practical synthesis of 2'F-araNs. Subsequently, we found an effect of additives on the direct phosphorylation of 1-bromide (4) with orthophosphoric acid. Tetra-n-butylammonium iodide was the most effective for achieving high alpha-selectivity among these additives. This reaction will be applicable for large-scale synthesis, and some 2'F-araNs were actually obtained in 30-40% yields from 1-O-benzoate (3). Thus, we proved the potency of the chemo-enzymatic synthesis of 2'F-ANs (2) by the use of alpha-1-phosphate (1).
Yamada
Kohei
K
Biochemicals Division, Yamasa Corporation, 10-1 Araoichio 2-Chome, Choshi, Chiba 288-0056, Japan.
Matsumoto
Noritake
N
Hayakawa
Hiroyuki
H
D001087:Arabinonucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D001419:Bacteria / Q000201:enzymology; D010430:Pentosyltransferases / Q000378:metabolism*; D011684:Purine Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry
D001087:Arabinonucleosides; D011684:Purine Nucleosides; D010430:Pentosyltransferases; C067995:nucleoside phosphorylase