Synthesis of 2'-amino-LNA: A new strategy

C. Rosenbohm, S.M. Christensen, M.D. Sørensen, D.S. Pedersen, L.-E. Larsen, J. Wengel, T. Koch

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Abstrakt

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.

OriginalsprogEngelsk
TidsskriftOrganic & Biomolecular Chemistry
Vol/bind2003
Udgave nummer4
Sider (fra-til)655-663
ISSN1477-0520
DOI
StatusUdgivet - 2003

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Citationsformater

Rosenbohm, C., Christensen, S. M., Sørensen, M. D., Pedersen, D. S., Larsen, L-E., Wengel, J., & Koch, T. (2003). Synthesis of 2'-amino-LNA: A new strategy. Organic & Biomolecular Chemistry, 2003(4), 655-663. https://doi.org/10.1039/B208864A