Method for preparing 3′-o-amino-2′-deoxyribonucleoside-5′-triphosphates

A method of preparing 3′-O-amino-2′-deoxyribonucleoside-5′-triphosphates comprising the steps of:

• (a) protecting a 5′-hydroxy group of a 2′-deoxyribonucleoside;
• (b) converting an (S)-3′-hydroxy group of the compound obtained in step (a) into an (R)-3′-hydroxy group;
• (c) reacting the product of step (b) with an N-hydroxyphthalimide to produce a 5′-O-protected-3′-O-phthalimido-2′-deoxynucleoside;
• (d) deprotecting the 5′-hydroxy group of the product of step (c);
• (e) converting the product of step (d) to a 3′-O—(N-acetone-oxime)-2′-deoxynucleoside;
• (f) triphosphorylating the 5′-hydroxy group of the product of step (e) to give a 3′-O—(N-acetone-oxime)-2′-deoxynucleotide triphosphate;
• and
• (g) converting the product of step (f) to a 3′-O-amine-2′-deoxynucleotide triphosphate by treating the product of step (f) with an aryl-oxyamine selected from the group consisting of O-benzylhydroxylamine, O-benzylhydroxylamine substituted with halo or methoxy, substituted or unsubstituted O-benzyloxyethylhydroxylamine, O-benzylhydroxylamine, O-[(2-Methoxyphenyl)methyl]hydroxylamine, O-[(3,5-Dichlorophenyl)methyl]hydroxylamine, O-(3-Chlorobenzyl)hydroxylamine, O-(4-Methoxybenzyl)hydroxylamine, O-[(3,4-Dichlorophenyl)methyl]hydroxylamine, O-(2-Chlorobenzyl)hydroxylamine, O-[4-(Trifluoromethyl)benzyl]hydroxylamine, O-[(2,5-Dichlorophenyl)methyl]hydroxylamine, O-(2-Methylbenzyl)hydroxylamine, O-(2,3,4,5,6-Pentafluorobenzyl)hydroxylamine, O-(2-(Benzyloxy)ethyl)hydroxylamine, O-(4-Bromophenyl)hydroxylamine, O-[2-(Trifluoromethyl)phenyl]hydroxylamine, and O-(2-Phenoxyethyl)hydroxylamine.