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. 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.
Rosenbohm
Christoph
C
Cureon A/S, Fruebjergvej 3, DK-2100 Copenhagen, Denmark.
Christensen
Signe M
SM
Sørensen
Mads D
MD
Pedersen
Daniel Sejer
DS
Larsen
Lotte-Emilie
LE
Wengel
Jesper
J
Koch
Troels
T
D003500:Cyclization; D007202:Indicators and Reagents; D009690:Nucleic Acid Conformation; D013936:Thymidine / Q000031:analogs & derivatives*
D007202:Indicators and Reagents; D013936:Thymidine