Locked nucleic acids: synthesis and characterization of LNA-T diol

Locked nucleic acids (LNAs) are RNA derivatives that have an O-methylene linkage between the 2 and 4 positions of the ribose. This leads to exceptionally high-affinity binding to complementary sequences. LNAs are synthesized from a commercially available sugar, 1,2:5,6-di-O-isopropylidene-a-D-allofuranose. An efficient and simplified procedure is presented for synthesizing a glycol donor that can be used for synthesis of a variety of LNA monomers. Then, as an example, the synthesis of the thymidine analog of LNA from this glycol donor is presented. The protocols give high yields of the desired products and avoid the use of time-consuming column chromatography.