Cleavage benzyloxycarbonyl esters

Stem bromelain is able to interact with two or more sequential amino adds in a peptide substrate, demonstrated by using A -benzyloxycarbonyl-L-phenylalanyl-L-serine methyl ester [36]. A glutamic add residue in position P3 prevents cleavage of the susceptible peptide braid. The sequences containing negatively charged residues in position P3 and P4 remain intact [37]. 

The final step in the solution-phase synthesis is to deprotect the N terminus of the completed peptide. The N-terminal amide bond must be cleaved without breaking any of the peptide bonds in the product. Fortunately, the benzyloxycarbonyl group is partly an amide and partly a benzyl ester, and hydrogenolysis of the benzyl ester takes place under mild conditions that do not cleave the peptide bonds. This mild cleavage is the reason for using the benzyloxycarbonyl group (as opposed to some other acyl group) to protect the N terminus. 

An important application of hydrogenating ester cleavage is involved in Bergmann s benzyloxycarbonyl method of synthesizing peptides.79 In this an amino acid is treated with benzyl chloroformate and then coupled with another amino acid molecule the benzyl group of the resulting benzyl carbamate residue produced is finally removed as toluene, the carbamic acid derivative that results decomposing immediately to carbon dioxide and the desired peptide ... 

Cleavage of p-nitrobenzyl group. Protection of carboxylic acids and amines as the esters and carbamates can take advantage of the selective reduction-induced fragmentation by zinc dust, as C=C bonds, S-N bonds, benzyloxycarbonyl, and diphenylmethyl groups are not affected during the operation. 

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