Protection phenylhydrazide

The reaction was applied to model dipeptides exemplified by the y-phenyl-hydrazide of N-carbobenzoxy-a-L-glutamyl-L-methionine methyl ester (4) and found to afford the carboxylic acid (S) in good yield without disturbance of the carbo-benzoxy and ester protective groups. The results suggest use of the phenylhydrazide group for protection of carboxyl groups in peptide chemistry. 

After removal of the protecting group (PG) from 134, the system was amenable to the oxidation/nucleophilic substitution process. Since this hnker represents a reversal of the original phenylhydrazide hnker, the traceless part stayed on the sohd support and the desired compound 135 was released. The utility of the linker was demonstrated in the synthesis of mono-ketopiperazines resulting from a cyclative cleavage. 

Recently, phenylhydrazide has been introduced as an enzyme-labile carboxy protecting group1122, 123]. This protecting group can be removed by mild enzymatic oxidation using a peroxidase1122, 1231 or mushroom tyrosinase11241 (Fig. 18-14). 

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