Improved synthesis of 2'-amino-LNA.

2'-Amino-LNA phosphoramidite (10) was synthesised by means of a new strategy, which is convergent with the synthesis of 2'-oxy-LNA up until a late stage intermediate (1).

Synthesis of 2'-amino-LNA: a new strategy.

In this paper we present revised and significantly improved synthetic routes to 2'-amino-LNA (locked nucleic acid). The optimal route is convergent with the synthesis of LNA monomers ("2'-oxy-LNA") via a common intermediate obtained by a mild deacetylation for the liberation of the 2'-hydroxy group to give compound 23 without the concomitant ring closure that affords the 2'-oxy-LNA skeleton. After inversion of the stereochemistry at C2' and triflate formation at the 2'-hydroxy group a new common intermediate 16 is obtained which gives easy access to a range of other analogues exemplified by the introduction of a sulfur nucleophile leading to the 2'-thio-LNA structure.