Synthesis of nucleoside mono-, di-, and triphosphoramidates from solid-phase cyclosaligenyl phosphitylating reagents.
Chloromethyl polystyrene resin was reacted with 5-hydroxysalicylaldehyde in the presence of potassium carbonate to afford polymer-bound 2-hydroxybenzaldehyde. Subsequent reduction with borane solution produced polymer-bound 2-hydroxybenzyl alcohol. The reaction of immobilized 2-hydroxybenzyl alcohol with appropriate phosphitylating reagents yielded solid-phase cycloSaligenyl mono-, di-, and triphosphitylating reagents, which were reacted with unprotected nucleosides, followed by iodine oxidation, deprotection of cyanoethoxy groups, and the basic cleavage, respectively, to afford 5'-O-nucleoside mono-, di-, and triphosphoramidates in 52-73% overall yield.
Ahmadibeni
Yousef
Y
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, The University of Rhode Island, Kingston, Rhode Island 02881, USA.
Tiwari
Rakesh K
RK
Sun
Gongqin
G
Parang
Keykavous
K
D000447:Aldehydes / Q000737:chemistry; D001592:Benzyl Alcohols / Q000737:chemistry; D002384:Catalysis; D007202:Indicators and Reagents; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D010084:Oxidation-Reduction; D011137:Polystyrenes / Q000737:chemistry
D000447:Aldehydes; D001592:Benzyl Alcohols; D007202:Indicators and Reagents; D009705:Nucleosides; D009943:Organophosphorus Compounds; D011137:Polystyrenes; C013243:salicylaldehyde