Reductive amination with tritylamine as an ammonia equivalent: efficient preparation of the 5-(4-(9-fluorenylmethyloxycarbonyl)aminomethyl-3,5-dimethoxyphenoxy)valeric acid (PAL) handle for peptide synthesis

N-Alkylation Reactions and Indirect Formation of Amino Functionalities in Solid-Phase Synthesis

“…[63][64][65][66][67][68][69][70][71][72][73][74][75][76][77] Also, reductive amination has been applied in the synthesis of libraries of artificial glycopeptides (2 × 96 members) 78 and carbohydrate mimetics (1088 members) 79 as well as for immobilization of oligonucleotides in micro-array preparation. 80 Linkers 8 and 14 with structures analogous to the 'PAL handle' (7, Scheme 2), 81,82 which was originally applied in the synthesis of C-terminal peptide amides, were independently applied in SPS by two groups in the mid-1990s. Ellman and co-workers prepared libraries of 1,4-benzodiazepine-2,5-diones 13 (62-93% yields, Scheme 3), 83,84 while Barany and co-workers reported on the synthesis of C-terminal modified peptide analogues and cyclic peptides, using the Backbone Amide Linker (BAL) strategy.…”

5-[(4-Aminomethyl)-3,5-dimethoxyphenoxy]pentanoic Acid

“…Removal of the Fmoc moiety with piperidine in DMF liberates the free amine prior to loading (eq 1). N-Substituted PAL resins have also been prepared by reductive amination of the backbone amide linker (BAL) resin using borohydride reagents such as NaBH(OAc) 3 13-15 and NaBH 3 CN 16 (eq 2). Solid-Phase Peptide Synthesis.…”

Functionalization of peptides and proteins by aldehyde or keto groups

“…Barany and co‐workers investigated the conception of solid‐phase synthesis handles, especially the tris(alkoxy)benzylamide (PAL) system 40–43. They recently described the Backbone Amide Linker (BAL) anchor,44 which can be used for the generation of peptide aldehydes.…”