Abstract
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. After substitution of the triflate with azide a basic reduction affords the desired 2′-amino-LNA structure, i.e., compound 18. This new synthesis strategy towards 2′-amino-LNA improves the overall yield significantly and converges the syntheses of 2′-oxy-LNA and LNA analogues.
Originalsprog | Engelsk |
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Tidsskrift | Organic and Biomolecular Chemistry |
Vol/bind | 1 |
Udgave nummer | 4 |
Sider (fra-til) | 655-663 |
Antal sider | 9 |
ISSN | 1477-0520 |
DOI | |
Status | Udgivet - 2003 |
Udgivet eksternt | Ja |