A new type of nucleotide analogue with 4-pyridylphosphonate internucleotide linkage

Tetrahedron Letters

Volumn 40, Issue 22, 1999, Pages 4263-4266

  Kers, Annika ^a   Stawiński, Jacek ^a  

^a STOCKHOLM UNIVERSITY   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; NUCLEOTIDE DERIVATIVE; PHOSPHORIC ACID DERIVATIVE; PYRIDINE NUCLEOTIDE; THYMIDINE DERIVATIVE;

ARTICLE; CHEMICAL BOND; CHIRALITY; DIASTEREOISOMER; STEREOISOMERISM; STRUCTURE ANALYSIS; SYNTHESIS;

EID: 0033612357     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(99)00702-9     Document Type: Article

References (22)

1. Zamecnik, P. C.; Stephenson, M. L. Proc. Natl. Acad. Sci. USA 1978, 75, 280-284.
2. De Mesmaeker, A.; Häner, R.; Martin, P.; Moser, H. E. Account Chem. Res. 1995, 28, 366-374.
3. Agrawal, S.; Zhao, Q. Current Opinion Mol. Biol. 1998, 2, 519-528.
4. Miller, P. S.; Yano, J.; Carrol, C.; Jayaraman, K.; Ts'o, P. O. P. Biochemistry 1979, 18, 5134-5143.
5. Miller, P. S. Non-ionic antisense oligonucleotides. In Oligodeoxynucleotides-Antisense Inhibitors of Gene Expression; J. S. Cohen, Ed.; The Macmillan Press Ltd.: New York, 1989; pp. 79-95.
6. Fathi, R.; Huang, Q.; Coppola, G.; Delaney, W.; Teasdale, R.; Krieg, A. M.; Cook, A. F. Nucleic Acids Res. 1994, 22, 5416-5424.
7. Engels, J. W.; Löschner, T.; Frauendorf, A. Nucleosides Nucleotides 1991, 10, 347-350.
8. Marugg, J. E.; De Vroom, E.; Dreef, C. E.; Van Der Marel, G. A.; Van Boom, J. H. Nucleic Acids Res. 1986, 14, 2171-2185.
9. Seela, F.; Kretschmer, U. J. Org. Chem. 1991, 56, 3861-3869.
10. Agarwal, K. L.; Riftina, F. Nucleic Acids Res. 1979, 6, 3009-3024.
11. Kers, A.; Stawinski, J.; Dembkowski, L.; Kraszewski, A. Tetrahedron 1997, 53, 12691-12698.
12. De Vroom, E.; Dreef, C. E.; Van Den Elst, H.; Van Der Marel, G. A.; Van Boom, J. H. Recl. Trav. Chim. Pays-bas 1988, 107, 592-595.
13. Huszthy, P.; Lempert, K.; Simig, G.; Tamas, J.; Hegedüs-Vajda, J. J. Chem. Soc., Perkin Trans. II 1985, 491-498.
14. Bidan, G.; Genies, M. Tetrahedron Lett. 1978, 2499-2502.
15. This reaction is thus related to that reported by D. Redmore who observed the formation of dialkyl 4- pyridylphosphonates upon heating at reflux for 2 h of triphenylmethylpyridinium tetrafluoroborate with a sodium salt of dialkyl phosphite in the corresponding dialkyl H-phosphonate as a solvent. Yields: 30-39%. See, Redmore, D. J. Org. Chem. 1976, 41, 2148-2150.
16. The different pathways for the reaction of DMT-C1 vs Tr-Cl with diphenyl H-phosphonate in pyridine are probably due to different stability of the corresponding carbocations generated in pyridine. The less stable trityl cation forms apparently stronger complexes with pyridine and facilitates nucleophilic attack by DPP on the 4-position of the pyridine ring. The dimethoxytrityl cation, on the other hand, due to the presence of electron-donating methoxy groups on the aromatic rings is much more stable and thus forms, most likely, rather weak complexes with pyridine. See also, Evans, A. G.; Price, A.; Thomas, J. H. Trans. Faraday Soc. 1956, 52, 332-344.
17. 31P NMR analysis (A. Kers, L. Dembkowski, A. Kraszewski, and J. Stawinski, manuscript in preparation).
18. The transformation of the dihydropyridine intermediate 2 to the 4-pyridylphosphonate 3 can be effected by the addition of few equivalents of iodine to the reaction mixture.
19. 4.
20. Stawinski, J.; Strömberg, R.; Zain, R. Tetrahedron Lett. 1992, 33, 3185-3188.
21. Due to low solubility of Tr-Br in pyridine, the reaction was heterogeneous and required several of hours for its completion.
22. CP)]: 6c- 15-4 ppm; 7.83-8.83 ppm (4H); 6.29 ppm (2H); 138.79 ppm (190.6 Hz), 137.84 ppm (7.3 Hz), 150.65 ppm (12.8 Hz). 6d, 16.3 ppm; 7.77-8.79 ppm (4H); 6.19 & 6.28 ppm (2H); 137.80 ppm (188.8 Hz), 137.84 ppm (11.0 Hz), 151.05 ppm (12.8 Hz).