Orthogonal amide ligation

In thiazolidine ligation, the reaction is performed between a glycolaldehyde peptide ester and an A/ -cysteinyl peptide. The capture step is based on 

Hgure4. Pseudoproline formation at the ligation side by a C-terminal aldehyde peptide reacting with a 1,2-aminothiol peptide at acidic pH. The reactive carboxyl and amino termini are positioned in close proximity for spontaneous peptide bond formation through an entropy-driven intramolecular 0- Alacyl transfer. 

Another method based on the same principle has been developed for the 

The enzymatic synthesis is fast and is completed in 15 min. After purification, the peptide obtained, with an acetal-protected aldehyde ester at its C-terminus, is treated with 95% TFA/H2O for 5 min to release the aldehyde function. 

Add sodium carbonate (0.2 g) to a suspension of chloromethyl polystyrene resin (0.5 g, 0.35 mmol) in DMSO (3 ml). Stir for 7 h at 155°C. This gives the benzaldehyde resin. 

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Bode et al. devised a unique chemoselective amide ligation by the decarboxylative condensations of a-ketoacids and A -alkylhydroxylamines (KAHA ligation) (Scheme 12) [64, 150-154]. This process requires neither coupling reagents nor catalysts, produces only water and carbon dioxide as by-products, and tolerates unprotected amino acid functional groups. It is also completely orthogonal to NCL and theoretically can be utilized at any junction. However, the limited access to A-alkylhydroxylamines and a-ketoacids restricts broader application of this chemistry. 

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