BRIDGED NUCLEOSIDES AS BUILDING BLOCKS OF OLIGONUCLEOTIDES: SYNTHESIS AND PROPERTIES

摘要

Bridging between the 2'- and 4'-carbons in a nucleoside restricts the furanose ring to C3'-endo conformation, which coincides with the sugar conformation in an oligonucleotide forming a duplex with single-stranded RNA (ssRNA) and a triplex with double-stranded DNA (dsDNA). Therefore, oligonucleotides modified by 2',4'-bridged nucleosides generally increase hybridization ability with ssRNA and dsDNA when compared with the natural oligonucleotide. Till date, a large number of 2',4'-bridged nucleosides with additional two-atom to four-atom bridges between 2'- and 4'-carbons have been developed by many research groups including our group. For this, ionic cyclization, ring-closing metathesis, and radical cyclization have been used so far as the synthetic strategies of bridge constructions. Based on such a background, we recently proposed a 2',4'-bridged nucleoside possessing 6'-oxygen founded on a new design concept and several types of analogs including 2'-O,4'-C-ethyleneoxy-bridged 5-methyluridine with a four-atom bridge have been developed. In addition, as a new strategy of bridge construction, radical cyclization using the 4'-carbon radical of a nucleoside was exemplified and a promising 2',4'-bridged nucleoside, the 6'-methyl analog of 2'-O,4'-C-ethylene-bridged 5-methyluridine, was found. This review mainly focuses on our recent results on bridged nucleosides used for chemically modified oligonucleotides. It describes the design and synthesis of the bridged nucleosides, along with the properties of oligonucleotides including bridged nucleosides.