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Chapter 6
peptide 1 and the PNA trimer 2 were purified by RP-HPLC and characterized by ESI-mass
spectrometry.
A Boc submonomer strategy was used for the modified PNA 3, in order to better preserve the
optical purity at the 2 position 30 . The submonomers were prepared from the corresponding
commercial Boc-L-amino acids suitably protected on the side chains. The Boc-L-Lysine-(2-
Cl-Z)-OH, to be used as synthon for inserting the lysine side chains in positions 5, was
transformed in the corresponding Weinreb amide and then reduced to the aldehyde. Boc-L-
Lys-(2-Cl-Z)-OH, Boc-L-Arg-(Tos)-OH and Boc-L-Val were transformed in the
corrsponding methyl esters and Boc deprotected by using HCl/MeOH. The PNA backbones
were then synthesized by reductive amination on L-amino acid methyl esters with the Boc-L-
Lys-(2-Cl-Z) aldehyde. The methyl esters were hydrolyzed and the secondary amines were
protected by the introduction of a Fmoc group. All the compounds were characterized by 1 H
and 13 C NMR and ESI mass spectrometry.
According to the previously reported procedures30, the chiral submonomers units were
inserted by manual coupling with the HATU/DIEA protocol on a MBHA-PS resin and, after
Fmoc deprotection, the nucleobase residues were introduced by a double coupling with
DIC/DhBTOH. After the cleavage from the resin, the PNA trimer 3 was purified by RP-
HPLC and characterized by ESI-mass spectrometry (Figure 6-4).
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