Reactions of 3'-C-Halomethyl and 3'-C-Sulfonylmethyl Uridines with Phosphinic Acid Derivatives - Synthesis of Building Blocks for Oligonucleotides Containing 3'-C-Methylenephosphonate Linkages

摘要

An efficient method for the synthesis of nucleoside 3'-C-methylenepnosphinates, building blocks for oligo(ribo-nucleoside methylenephosphonate)s, building blocks for oligo(ribo-nucleoside methylenephosphonate)s, has been developed. Treatment of bis(trimethylsilyl)hypophosphite (BTSP) with a 3'-deoxy-3-C-(iodomethyl)uridine resulted both in substitution to give the corresponding 3'--C-methylenephosphinate and in reduction of the iodomethyl group to afford the uridine 3'-deoxy-3'-C-methyl derivative. Optimisation of solvent and tempeature gave a substitution/reduction ratio of 5:4 at best. Through the use of a trifluoromethanesulfonyl leaving group and further optimisation of reaction conditions, however, the triethylammonium 2'-O-(tert-butyldimethylsilyl)-3'-deoxy-5'-O-(4-methoxytriphenylmethyl)uridine-3'-C-methylene-phosphinate was obtained in 93% isolated yield.