Synthesis of polyamide nucleic acids (PNAs) using a novel Fmoc/Mmt protecting-group combination

PNA: Synthetic Polyamide Nucleic Acids with Unusual Binding Properties

“…B) Synthesis of adenyl acetic acid via the N 6 -protected adenine. [20,25,26] also proceeds smoothly. The resulting protected adenine derivatives are then N 9 -alkylated with methyl or tert-butyl bromoacetate.…”

“…amination with glycine esters and protected aminoacetaldehyde [23,24] ( Figure 2B), and reductive amination using 1,2-diaminoethane and glyoxylic acid [25,26] ( Figure 2C). Further reaction steps lead to protected aminoethylglycine derivatives with unprotected secondary amino groups to which the nucleobase acetic acid derivatives can be coupled.…”

“…In this case, the reaction with Cbz-Cl is unproblematic. [20] Introduction of the Mmt [25] or anisoyl groups [26] in pyridine Figure 5. A) Synthesis of Cbz-protected adenyl acetic acid according to Dueholm et al: [27] a) BrCH 2 COOEt, NaH, DMF; b) N-(benzyloxycarbonyl)-N'-ethylimidazolium tetrafluoroborate, DMF, CH 2 Cl 2 ; c) NaOH (aq.).…”

“…B) Synthesis of Boc ± Aeg derivates by reductive amination from Boc-aminoacetaldehyde and glycine esters. C) Synthesis of Aeg derivates by reductive amination from 1,2-diaminoethane and glyoxylic acid: [25,26] a) H 2 /Pd/C, H 2 O; b) MeOH/HCl; c) Mmt-Cl, DMF, NEt 3 ; d) Fmoc-(ONSu), dioxane/H 2 O; e) MeOH/HCl.…”

“…the first step by using the appropriate acid chloride or Mmt chloride in pyridine. The resulting benzyloxycarbonyl, [9,20,27] 4-tert-butylbenzoyl, anisoyl, [22,26] and Mmt derivatives [25] are then N 1 -alkylated with methyl bromoacetate [25±27] or tert-butyl bromoacetate [20] . Finally, cleavage of the ester group under basic or acidic conditions gives the corresponding cytosyl acetic acid derivative.…”