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Synthesis of a peptide nucleic acid with a novel 1‐methyl‐6‐mercaptopurine base
Author(s) -
AboulFadl Tarek,
Rajeev Gopalan,
Broom Arthur D.
Publication year - 2008
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570450223
Subject(s) - chemistry , peptide nucleic acid , monomer , pyridine , reductive amination , hydrolysis , peptide , acetic acid , lysine , nucleic acid , chloride , polymer chemistry , medicinal chemistry , organic chemistry , stereochemistry , combinatorial chemistry , amino acid , catalysis , biochemistry , polymer
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% CCl 4 in pyridine and Ph 3 P. 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 NaBH 3 CN 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% CCl 4 in DCM in the presence of Ph 3 P.