Scheme 1.

Synthesis of 2-thiouracil PNA monomer. (a) 4-Methoxybenzyl chloride in alkaline (KOH) water/EtOH (1:1). (b) Ethyl bromoacetate in ethanolic sodium ethoxide followed by precipitation from ethyl acetate. (¹H nuclear Overhauser enhancement NMR analysis and comparison of the ¹³C NMR spectrum with reports in the literature of N-alkylated S-benzylthiouracils (13) confirmed the assignment of the desired product (N¹-alkylation.) (c) LiOH in water/MeOH/tetrahydrofuran (THF) (1:3:7). (d) Ethyl N-(2-Boc-aminoethyl)glycinate/O-benzotriazole-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU) in dimethylformamide. (e) LiOH in water/MeOH/THF (1:3:7).