Synthesis of 4'-C-phenylselenated deoxyribonucleosides by radical epimerization

Tetrahedron Letters

Volumn 38, Issue 15, 1997, Pages 2657-2660

  Wackernagel, Felix ^a   Schwitter, Urs ^a   Giese, Bernd ^a  

^a UNIVERSITY OF BASEL   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

DEOXYRIBONUCLEOSIDE;

ARTICLE; CHIRALITY; DRUG SYNTHESIS; IN VITRO STUDY;

EID: 0031002789     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)00449-8     Document Type: Article

References (16)

1. B. Giese, A. Dussy, C. Elie, P. Erdmann, U. Schwitter, Angew. Chem. Int. Ed. Engl. 1994, 33, 1861. B. Giese, P. Erdmann, T. Schäfer, U. Schwitter, Synthesis 1994, 1310.
2. B. Giese, A. Dussy, C. Elie, P. Erdmann, U. Schwitter, Angew. Chem. Int. Ed. Engl. 1994, 33, 1861. B. Giese, P. Erdmann, T. Schäfer, U. Schwitter, Synthesis 1994, 1310.
3. B. Giese, X. Beyrich-Graf, P. Erdmann, M. Petretta, U. Schwitter, Chem. & Biol. 1995, 2, 368.
4. 3CN as we had already shown for a differently protected thymidine derivative. 4
5. B. Giese, P. Erdmann, L. Giraud, T. Göbel, M. Petretta, T. Schäfer, M. von Rauner, Tetrahedron Lett. 1994, 35, 2683.
6. 1H NMR (0.25-0.55 ppm) of the pyrimidine proton 6-H in the deoxyribonucleosides 7a and 8a compared to 7b and 8b, respectively.
7. Extended irradiation of 8b yielded 5 new peaks in HPLC. By separation of 3 peaks the disproportionation products 10a,b and 11a,b were identified (NMR). The two remaining HPLC peaks might correspond to the recombination products.
8. -1: M. Newcomb, Tetrahedron 1993, 49, 1151; G. A. Russell, H. Tashtoush, J. Am. Chem. Soc. 1983, 105, 1398. Because of the low steady state concentration of the PhSe radical, the formation of the selenides 7a,b and 8a,b via combination of the 4'-alkyl radicals with the PhSe radical seems to be less important.
9. -1: M. Newcomb, Tetrahedron 1993, 49, 1151; G. A. Russell, H. Tashtoush, J. Am. Chem. Soc. 1983, 105, 1398. Because of the low steady state concentration of the PhSe radical, the formation of the selenides 7a,b and 8a,b via combination of the 4'-alkyl radicals with the PhSe radical seems to be less important.
10. The epimeric selenides exhibit the same UV spectra so that the thermal and not the photochemical equilibrium is reached.
11. A prerequisite of a radical epimerization is the reversible formation of the C,X-bond. This is the case for example for C,Co- and C,I-bonds: A. Ghosez, T. Göbel, B. Giese, Chem. Ber. 1988, 121, 1807; H. Sugiyama, K. Fujimoto, I. Saito, J. Am. Chem. Soc. 1995, 117, 2945.
12. A prerequisite of a radical epimerization is the reversible formation of the C,X-bond. This is the case for example for C,Co- and C,I-bonds: A. Ghosez, T. Göbel, B. Giese, Chem. Ber. 1988, 121, 1807; H. Sugiyama, K. Fujimoto, I. Saito, J. Am. Chem. Soc. 1995, 117, 2945.
13. J. March in Advanced Organic Chemistry, J. Wiley, New York, 1985, p.528.
14. 2 (0.9 mmoles) in toluene (80 ml) was saturated with Ar and irradiated (150 W, Heraeus Hg-high pressure lamp) at 15°C. After 5-7h of irradiation the solvent was evaporated and the isomers separated by flash chromatography (silicagel; AcOEt:hexane = 2:1 to 3:1 as eluent). Under these conditions the isomer ratio (7a:7b and 8a:8b) was about 1:1. The yields for each of the isolated isomers were 35-47%.
15. 2 group was benzoylated, and the 3'-OH convened into the phosphoramidites.
16. m) were determined in medium salt buffer (100 mM NaCl; 10 mM phosphate buffer pH=7; 0.1 mM EDTA; λ = 260 nm) as the maximum of the first derivative of the melting curve. A temperature gradient of 1 °C/min was applied.