Spin Labeled Nucleoside Analogues: 4′-Hydroxymorpholin-2′-Ylpurines and Pyrimidines

Upon borane-pyridine reduction, a series of nucleoside dialdehyde dioximes 2 underwent cyclization to the corresponding 4′-hydroxymorpholin-2′-ylpurines or pyrimidines 3 from which the peracetyl derivatives 4 were prepared. At room temperature, compounds 3 and 4 exist as a mixture of invertomers in which the 4′S (equatorial 4′-OH or 4′-OAc) predominates. A 14 kcal/mol, nitrogen inversion barrier was estimated from variable temperature experiments. N.O.E. and 3 J CH measurements established the anti conformation of the base-"sugar" bond. Compounds 3 spontaneously oxidized to the corresponding aminoxyl free radicals, EPR spectra of which showed that they existed in a chair conformation.