SYNTHESIS OF 5'-O-AMINO-2'-DEOXYPYRIMIDINE AND PURINE NUCLEOSIDES - BUILDING-BLOCKS FOR ANTISENSE OLIGONUCLEOSIDES

An efficient synthesis of 5'-O-amino-2'-deoxy analogs of uridine 1, th ymidine 2, cytidine 3, 5-methylcytidine 3a, adenosine 4, and guanosine 5 was accomplished. The key step of 5'-O-N-bond formation in 2'-deoxy nucleosides 1-5 was achieved via a Mitsunobu reaction in excellent yie lds. The 5'-O-amino nucleosides 1-5 are useful building-blocks for the synthesis of nucleoside dimers linked by a methylene(methylimino) (MM I) bridge. MMI is a novel phosphate surrogate for antisense oligonucle osides.