404384-16-3Relevant academic research and scientific papers
Substituent and solvent effects of TMS triflate mediated C1′ epimerization of β-thymidine to α-thymidine
Sato, Yuichi,Tateno, Gohsuke,Seio, Kohji,Sekine, Mitsuo
, p. 87 - 93 (2007/10/03)
This paper deals with kinetic studies of TMSOTf-mediated C1′ epimerization of β-thymidine to α-thymidine. The effect of neighboring group participation by various 5′-hydroxy protecting groups, such as toluoyl, Et2CHC(O), Et2NC(O), and Et2NC(S), on the β→α conversion is described in detail. The time dependence of the ratio of the α and β anomers in the C1′ epimerization was estimated by 1H NMR. The α/β equilibrium constants K and the rate constants kα and kβ were calculated on the basis of the experimental data. As the result, it was concluded that, in acetonitrile, the α/β equilibrium constants K are thermodynamically affected by steric hindrance from the 5′-hydroxy protecting group. On the other hand, the rate constants kα and kβ are mainly influenced by the stability of the oxonium ion intermediate. In particular, formation of an intramolecularly cyclized iminium ion intermediate from the oxonium ion intermediate, due to the neighboring group participation by the diethylthiocarbamoyl group, tended to decrease the overall reaction rate. Finally, the α/β C1′ epimerization could be carried out with a high α anomer selectivity of 89% through the use of the Et2CHC(O) group. Thus, 5′-O-pixyl-α-thymidine could be synthesized from β-thymidine as a key intermediate for the synthesis of α-DNA in a considerably improved overall yield of 40%.
