Benzyloxycarbonyl group peptide synthesis

BW Erickson, RB Merrifield. Use of chlorinated benzyloxycarbonyl protecting groups to eliminate Ne-branching at lysine during solid-phase peptide synthesis. J Am Chem Soc 95, 3757, 1973. 

K Kuromizu, J Meienhofer. Removal of the JW-benzyloxycarbonyl group from cysteine-containing peptides by catalytic hydrogenolysis in liquid ammonia, exemplified by a synthesis of oxytocin. J Am Chem Soc 96, 4978, 1974. 

AE Jackson, RAW Johnstone. Rapid, selective removal of benzyloxycarbonyl groups from peptides by catalytic transfer hydrogenation. Synthesis 685, 1976. 

Scheme 14 Synthesis of Tyrosine O-Sulfate Peptides with the Benzyloxycarbonyl Group for Temporary N -Protectionl41 ...

The first solid-phase peptide synthesis reported by Merrifield had some disadvantages, which were corrected in later versions of this synthesis. The main improvements were the replacement of benzyloxycarbonyl protective groups by the TFA-labile Boc protection, and the use of TFA-resistant linkers cleavable by HF. 

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. 

The invention of the benzyloxycarbonyl group by Bergman and Zervas in 1932121 was one of the milestones in the development of modem synthetic chemistry. This one group, perhaps more than any other, was the harbinger of the modern era of peptide synthesis and the versatility of the Cbz group ensures it a valued place amongst its many rivals. 

Due to the high stability of the benzyloxycarbonyl group under most conditions of peptide synthesis and its mild and selective hydrogenolytic cleavage, it is generally used for intermediate a-annino protection in chain-elongation steps in combination with the more acid-... 

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