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

摘要

A 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 N epsilon-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.