A Practical and Efficient Approach to PNA Monomers Compatible with Fmoc-Mediated Solid-Phase Synthesis Protocols

A straightforward synthesis of orthogonally protected PNA monomers is described. Protected aminoethylglycine (Aeg) monomers were efficiently prepared by reductive amination of N-Fmoc-glycinaldehyde with glycine methyl ester and the subsequent acylation of the free amine with N-bis-Boc-protected nucleobase acetic acids. The exocyclic amine group of the nucleobases, including the notoriously difficult-to-protect guanine nucleobase, was protected with a bis-Boc carbamate group; this increased the solubility of the nucleobases in the most common organic solvents. The current protocol allows all Aeg monomers to be prepared on both the micro- and macroscale, which avoids or minimizes the use of toxic reagents or solvents, and moreover, cheap starting materials are used. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)