A new approach to oligonucleotide N3′ → P5′ phosphoramidate building blocks

Tetrahedron Letters

Volumn 47, Issue 26, 2006, Pages 4495-4499

  Zielinska, Daria ^a   Pongracz, Krisztina ^a   Gryaznov, Sergei M ^a  

^a GERON CORPORATION   (United States)

Author keywords

3 Aminonucleosides; Phosphoramidates; Phosphoramidites

Indexed keywords

3' AMINO 2',3' DIDEOXYNUCLEOSIDE DERIVATIVE; 3' AMINONUCLEOSIDE 5' PHOSPHARAMIDITE DERIVATIVE; NUCLEOSIDE DERIVATIVE; OLIGONUCLEOTIDE; PHOSPHORAMIDOUS ACID DERIVATIVE; SUGAR; THIOPHOSPHORAMIDATE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG SYNTHESIS; METHODOLOGY;

EID: 33646769296     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2006.04.100     Document Type: Article

References (12)

1. Herbert B.-S., Pongracz K., Shay J.W., and Gryaznov S.M. Oncogene 21 (2002) 638-642
2. Ford L.P., Zou Y., Pongracz K., Gryaznov S.M., Shay J.W., and Wright W.E. J. Biol. Chem. 276 (2001) 32198-32203
3. Gryaznov S.M. Biochem. Biophys. Acta 1489 (1999) 131-140
4. Nelson J.S., Fearon K., Nguyen M.Q., McCurdy S.N., Frediani J.F., Foy M.F., and Hirschbein B.L. J. Org. Chem. 62 (1997) 7278-7287
5. The 3′-amino purine nucleosides: 3′-amino-2′, 3′-dideoxyadenosine and 3′-amino-2′, 3′-dideoxyguanosine were acquired from Metkinen Oy (Finland). These compounds were prepared by an enzymatic trans-glycosylation process starting from 3′-amino-3′-deoxythymidine, which was obtained via reduction of readily available 3′-azido-3′-deoxythymidine (AZT). 3′-Amino-2′,3′-dideoxycytidine was prepared as described:. Glinski R.P., Khan S.M., Kalamas R.L., and Stevens C.L. J. Chem. Soc. D (1970) 915-916
6. N- versus O-selective tritylation of aliphatic non-nucleoside-based amino alcohols was previously reported; for example:. Buckus P., Saboniene R., and Lemesiene D. Zh. Org. Khimi (Russian) 6 (1970) 1984-1987
7. 3), 149.48, 149.17, Rp/Sp-isomers.
8. 4-selective benzoylation: 4.7 g (10 mmol) of dry 3′-NH-Tr-2′,3′-ddC was dissolved in a mixture of 150 ml acetonitrile and 15 ml methanol. To this solution benzoic anhydride (13.6 g, 60 mmol) and triethylamine (1 ml) were added, and the reaction mixture was stirred at 50 °C for 2 h, and then at ambient temperature overnight. After evaporation in vacuo the resultant oil was dissolved in a small amount of methylene chloride and precipitated with hexane. The precipitation was repeated, and after drying in vacuo, the product was obtained as a light yellow foam (4 g, 69.6% yield).
9. + 334.
10. It was reported that diethylpyrocarbonate reaction with purine nucleotides within DNA or RNA nucleic acids yields similar type of products:. Leonard N.J., McDonald J.J., and Reichmann M.E. PNAS 67 (1970) 93-98
11. 1H NMR and TLC analyses.
12. 2-Tr-) tritylated compounds with the molar ratio of 1:1.9, respectively.