SYNTHESIS OF PHOSPHONATE ISOSTERES OF 2'-DEOXY-1',2'-SECO-NUCLEOTIDES

Practical and convergent syntheses of 2'-deoxy-1',2'-seco-nucleophosph onates and 1',2'-seco-nucleophosphonates are described. Phosphonate ch irons derived from D-isoascorbic acid were used in alkylation of funct ionalized nucleobases to provide the title phosphonate isosteres in go od yields. Subsequent deprotection and deesterification led to the 5'- C-methylenephosphonic acids which were conveniently purified using gra vity flow C-18 reverse phase column chromatography.