The thermal N-9/N-7 isomerization of N-2-acylated 2 `-deoxyguanosine derivatives in the melt and in solution

Abstract

The protected 2'-deoxyguanosine derivatives 5a - c undergo N-9 --> N-7 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 N-2.3'-O.5'-O-tris(4-toluoyl) derivative -% and the N-2-acetyl-3',5'-bis-O-[(tert-butyl)dimethylsilyl] derivative 5c gave anomeric mixtures of the,V-isomers 9b/10b) (43%) and 9c/10c (55%). respectively, In addition, the N-9-alpha-D-anomers 8b and 8c are obtained. Different from 5b, the isomerization of peracetylated 5a resulted in low yields. Compound 5b was also prone tu isomerization performed in solution (toluene. 100, 5 min: chlorobenzene, 120. 5 min). furnishing the N-7-regioisomers in 24-53% yield. The highest yield of the N-9 --> N-7 isomerization occurred in the presence of 2-deoxy-3,5-di-O-(4-toluoyl)-alpha-D-erythro-pentofuranosyl chloride.