Related Experiment Video
Updated: Jan 8, 2026

Solid Phase Synthesis of a Functionalized Bis-Peptide Using "Safety Catch" Methodology
Published on: May 15, 2012
On-Resin Pictet-Spengler Cyclization for 1,2,3,4-Tetrahydro-β-carboline-3-carboxylate (Tcc) Peptide Synthesis With
Omer S L N'dri1, Charity D Yongo-Luwawa1, Xiaozheng Wei1
1Département de Chimie, Université de Montréal, Montréal, Québec, Canada.
None:
The constrained tryptophan (Trp) analog 1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (Tcc) is used to restrict peptide conformation in structure-activity relationship studies. Although Pictet-Spengler cyclization of Trp and aldehydes with mineral acid gives Tcc analogs, such harsh conditions do not tolerate acid-labile functionality. To enable broader use of Tcc residues, mild conditions are now reported for the on-resin Pictet-Spengler cyclisation in the presence of acid-labile side chain protection and linker strategies.
Related Concept Videos
α-Bromination of Carboxylic Acids: Hell–Volhard–Zelinski Reaction
Acid Halides to Carboxylic Acids: Hydrolysis
As shown below, the mechanism involves a nucleophilic attack by water at the carbonyl carbon to form a tetrahedral intermediate. This is followed by the reformation of the carbon–oxygen π bond along with the departure of a halide ion. A final proton transfer step yields carboxylic...
Olefin Metathesis Polymerization: Ring-Opening Metathesis Polymerization (ROMP)
Alkylation of β-Diester Enolates: Malonic Ester Synthesis
Carboxylic Acids to Esters: Acid-Catalyzed (Fischer) Esterification Mechanism
Cationic Chain-Growth Polymerization: Mechanism

