N-pent-4-enoyl nucleosides: Application in the synthesis of support-bound and free oligonucleotide analogs by the H-phosphonate approach

Tetrahedron Letters

Volumn 37, Issue 10, 1996, Pages 1539-1542

  Iyer, Radhakrishnan P ^a   Devlin, Theresa ^a   Habus, Ivan ^a   Ho, Nan Hui ^a   Yu, Dong ^a   Agrawal, Sudhir ^a  

^a HYBRIDON INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

NUCLEOTIDE DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; NUCLEAR MAGNETIC RESONANCE; REACTION ANALYSIS; TECHNIQUE;

EID: 0029964222     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)00066-4     Document Type: Article

References (20)

1. (a) Uhlmann, E.; Peyman, A. Chem. Rev. 1990, 90, 544-584;
2. (b) Agrawal, S, Iyer, R. P. Curr. Op. Biotech. 1995, 6, 12-19.
3. Beaucage, S. L. in Methods in Molecular Biology: Protocols for Oligonucleotides and Analogs; Agrawal, S., Ed.; Humana Press: Totowa, New Jersey, 1993, Vol. 20, pp. 33-61.
4. Froehler, B. C. in Methods in Molecular Biology: Protocols for Oligonucleotides and Analogs; Agrawal, S., Ed.; Humana Press: Totowa, New Jersey, 1993, Vol. 20, pp. 63-80.
5. For application of PNT nucleosides in phosphoramidite chemistry, see Iyer, R. P.; Yu, D.; Ho, N-H.; Devlin, T.; Agrawal S. J. Org. Chem. 1995, 60, 8132-33.
6. (a) For elegant applications of the PNT group in the synthesis of carbohydrates see: Debenham, J. S.; Madsen, R.; Roberts, C.; Fraser-Reid, B. J. Am. Chem. Soc. 1995, 117, 3302-03 and references therein;
7. (b) For a review of protecting groups in oligonucleotide synthesis, see: Beaucage, S. L.; Iyer, R. P. Tetrahedron 1992, 48, 2223-2311.
8. (a) Ti, G. S.; Gaffney, B. L.; Jones, R. A. J. Am. Chem. Soc. 1982, 704, 1316-19;
9. (b) The analogs 1-3 were fully characterized (see ref. 4);
10. 12 Deprotection conditions are being optimized.
11. 31P-NMR and FAB-MS.
12. For details of HPLC conditions and analysis, see Iyer, R. P.; Yu, D.; Agrawal, S. Bioorg. Chem. 1995, 23, 1-21.
13. 3 (0.05 M in MeOH) can also be used for this purpose.
14. For recent efforts in the synthesis of methylphosphotriester Oligonucleotides see: Hayakawa, Y.; Hirose, M.; Hayakawa, M.; Noyori, R. J. Org. Chem. 1995, 60, 925-930 and references therein.
15. 2/pyridine/water reagent resulted in the formation of ca. 10% of the corresponding phosphoric diester product;
16. 260 units) with t-butylamine/water, 1/1 (1 ml, 55 °C, 4 h) or thiophenol resulted in its conversion, exclusively, to the corresponding diester product.
17. (a) Kuijpers, W. H. A.; Huskens, J.; Koole, L. H.; van Boeckel, C. A. A. Nucl. Acids Res. 1990, 18, 5197-5205;
18. (b) Conditions for cleavage from the support are being optimized.
19. Agrawal, S.; Mayrand, S.; Zamecnik, P. C.; Pederson T. Proc. Natl. Acad. Sci. (USA) 1990, 87, 1401-05.
20. T. Atkinson, S. Gillam, M. Smith, Nucl. Acids Res. 1988, 16, 6232.