Three-Dimensional Heterocycles: New Uracil-Based Structures Obtained by Nucleophilic Substitution at the sp(2) Carbon of Bromoisoxazoline

The regioisomeric cycloadducts of bromonitrile oxide and N-benzoyl-2,3-oxaza-norborn-5-ene were easily prepared and elaborated into a novel class of uracil-based scaffolds. The key-synthetic step is the nucleophilic substitution at the sp(2) carbon atom of the bromoisoxazoline three-dimensional heterocycles. The protocol to perform the nucleophilic substitution of uracil anions was optimized and adapted to the steric requirements of the substrates. A library of pyrimidine derivatives was prepared in very good yields and the products were fully characterized. They are proposed as nucleoside analogues and as synthons for β-turn motifs within PNA structures.