An improved method for the synthesis of N3' → P5' phosphoramidate oligonucleotides

Tetrahedron Letters

Volumn 38, Issue 2, 1997, Pages 207-210

  McCurdy, Sarah N ^a   Nelson, Jeffrey S ^a   Hirschbein, Bernard L ^a   Fearon, Karen L ^a  

^a ILLUMINA INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

OLIGONUCLEOTIDE;

ARTICLE; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; REACTION ANALYSIS; TECHNIQUE;

EID: 0031021880     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(96)02254-X     Document Type: Article

References (11)

1. Uhlman, E.; Peyman, A. Chem. Rev. 1990, 90, 544-584.
2. Gryaznov, S.; Chen, J.-K. J. Am. Chem. Soc. 1994, 116, 3143-3144.
3. Chen, J.-K.; Schultz, R. G.; Lloyd, D. H.; Gryaznov, S. M. Nucleic Acids Res. 1995, 23, 2661-2668.
4. Gryaznov, S. M.; Lloyd, D. H.; Chen, J.-K.; Schultz, R. G.; DeDionisio, L. A.; Ratmeyer, L.; Wilson, W. D. Proc. Natl. Acad. Sci. USA 1995, 92, 5798-5802.
5. Gryaznov, S.; Skorski, T.; Cucco, C.; Nieborwska-Skorska, M.; Chiu, C. Y.; Lloyd, D.; Chen, J.-K.; Koziolkiewicz, M.; Calabretta, B, Nucleic Acids Res. 1996, 24, 1508-1514.
6. The phosphoramidite amine-exchange method has previously been used to form from 1 to 3 P3′→N5′ phosphoramidate oligonucleotide linkages (Bannwarth, W. Helv. Chim. Acta 1988, 71, 1517-1527 and Gryaznov, S. M.; Letsinger, R. L. Nucleic Acids Res. 1992, 20, 3403-3409).
7. The phosphoramidite amine-exchange method has previously been used to form from 1 to 3 P3′→N5′ phosphoramidate oligonucleotide linkages (Bannwarth, W. Helv. Chim. Acta 1988, 71, 1517-1527 and Gryaznov, S. M.; Letsinger, R. L. Nucleic Acids Res. 1992, 20, 3403-3409).
8. The phosphoramidite amine exchange approach has been recently described (Schultz, R. G.; and Gryaznov, S. M. Nucleic Acids Res. 1996, 24, 2966-2973) for the synthesis of 2′-fluoro-2′-deoxynucleotide N3′→P5′ phosphoramidates in which the basicity of the 3′-amine is considerably lower than in this reported chemistry where the 2′ position is unfunctionalized.
9. Ibu, which is stable for 1 day only.
10. 5′-(N,N-diisopropylamino 2-cyanoethyl) phosphoramidite-3-O-dimethoxytrityl 2″-deoxynucleosides are available from Glen Research. A 90 s detritylation time with 3% dichloroacetic acid should be used.
11. 2O.