A Fmoc-based submonomeric strategy for the solid phase synthesis of optically pure chiral PNAs

A new submonomeric approach for the Fmoc solid phase synthesis of chiral PNAs is reported here. The design and synthesis of a new D-lysine-based Fmoc submonomer obtained by replacing the nucleobase residue with an Alloc group, compatible with Fmoc chemistry, is described starting from D-lysine and Fmoc-aminoacetaldehyde. The desired submonomer was obtained in high yield with no racemization. The conditions for synthesizing a chiral PNA dimer on solid support by a submonomeric approach have been optimized, allowing to obtain the desired PNA with a very high optical purity.