Synthesis of Nucleobase-Functionalized Morpholino Monomers

Abstract

Morpholino antisense oligonucleotides are used as routine tools in developmental biology to investigate gene function during early embryogenesis. These chemically modified oligos contain morpholine ring connected with phosphorodiamidate linkages as backbone but carry unmodified nucleobases. In this chapter, we describe the methods to further modify the nucleobases using palladium-catalyzed cross-coupling reactions. The key reactions used are halogenations of the nucleobases in suitable position and subsequent Pd-catalyzed Sonogashira and Suzuki reactions. The sequential synthetic steps are described in detail in this chapter, and the examples are shown in tables.

Keywords: Functionalized nucleobases; Halogenation; Morpholino monomers; Morpholino oligonucleotides; Pd-catalyzed cross-coupling.