Synthesis of morpholino nucleosides starting from enantiopure glycidol

Abstract

The synthesis of modified morpholino monomers was performed in a few steps through the condensation between 6-hydroxymethyl-morpholine acetal and nucleobases under Lewis acid conditions. The key common precursor of the targets – 6-hydroxymethyl-morpholine acetal – is easily synthesised via oxirane ring opening of optically pure glycidol using N-nosyl aminoacetaldehyde as a nucleophile, followed by an O-benzoylation/ring-closure tandem reaction sequence. Using readily available building blocks, this strategy allows access to diversified optically pure morpholino monomers in good yields and anomeric ratios.