The Thermal N9/N7 Isomerization of N2‐Acylated 2′‐Deoxyguanosine Derivatives in the Melt and in Solution

The protected 2′‐deoxyguanosine derivatives 5a – c undergo N⁹→N⁷ isomerization in the melt and in solution. The rate of isomerization is much faster than in the case of the corresponding ribonucleosides and occurs even in the absence of a catalyst. In the melt (195°, 2 min), the N²,3′‐O,5′‐O‐tris(4‐toluoyl) derivative 5b and the N²‐acetyl‐3′,5′‐bis‐O‐(tert‐butyl)dimethylsilyl] derivative 5c gave anomeric mixtures of the N⁷‐isomers 9b / 10b (43%) and 9c / 10c (55%), respectively. In addition, the N⁹‐α‐D ‐anomers 8b and 8c were obtained. Different from 5b , the isomerization of peracetylated 5a resulted in low yields. Compound 5b was also prone to isomerization performed in solution (toluene, 100°, 5 min; chlorobenzene, 120°, 5 min), furnishing the N⁷‐regioisomers in 24–53% yield. The highest yield of the N⁹→N⁷ isomerization occurred in the presence of 2‐deoxy‐3,5‐di‐O‐(4‐toluoyl)‐α‐D ‐erythro‐pentofuranosyl chloride.