Tuning Cross-Coupling Approaches to C3 Modification of 3-Deazapurines

Abstract

A general approach to C3 modification of purine scaffold through various types of cross-coupling reactions has been established. Tuning substrate electronics and reaction conditions resulted in the development of highly efficient sp2–sp, sp2–sp2, and sp2–sp3 cross-coupling conditions for modification of 3-deazaadenine to access C3-modified adenine and hypoxanthine scaffolds. The optimized methodologies to access the corresponding 3-deazaadenosine phosphoramidites for solid-phase DNA synthesis have been demonstrated.