Synthesis of a peptide nucleic acid with a novel 1‐methyl‐6‐mercaptopurine base

Abstract

Abstractmagnified imageA novel peptide nucleic acid (PNA) monomer 16 containing a novel 1‐methyl‐6‐mercaptopurine base was synthesized by coupling the in situ generated acid chloride of (1‐methyl‐6‐mercaptopurin‐9‐yl)acetic acid (6) into an L‐lysine backbone (13) using 10% CCl4 in pyridine and Ph3P. Compound 6 was synthesized from 6‐mercapto‐1‐methylpurine and ethylbromoacetate in the presence of NaH followed by alkaline hydrolysis and subsequent neutralization with a cation exchange resin. The L‐lysine backbone (13) was obtained by the reaction of Nϵ‐CBZ‐L‐lysine allyl ester with Boc‐aminoactaldehyde in the presence of NaBH3CN under reductive amination conditions. Oligomerization of the monomer 16 to PNA analogues was achieved using BOC‐BHA‐PEG‐PS resin as a solid support and the in situ generated acid chloride of 16 by 10% CCl4 in DCM in the presence of Ph3P.