Carbobenzoxy group

Ben-Ishai D, Berger A (1952) Cleavage of N-carbobenzoxy groups by dry hydrogen bromide and hydrogen chloride. J Org Chem 17 1564—1570... 

Fig. 18. The active site region of the electron density difference map between N-carbobenzoxy-L-alanine-elastase at —SS C and native elastase at the same temperature. The resolution is 3.5 A. The bilobed feature is consistent with the binding of the alanyi portion of the substrate to the oxygen of the catalytic serine, with weak interaction of the carbobenzoxy group to the surface of the enzyme.

Template oligomer synthesis was described by Bohmer and Kammerer. Using p-cresyl-formaldehyde oligomers as a frame of the template, esters of aminoacids were prepared. The reaction, which may be considered as a model of a template reaction, was studied in its simplest form, based on the synthesis of cyclic dimers. The process can be represented by the following set of reactions (R - carbobenzoxy group) ... 

This Pd catalyst is recommended for deblocking of carbobenzoxy groups by transfer hydrogenolysis (formic acid donor).7... 

To prevent side reactions, the amino group of alanine must be protected to make it nonnucleophilic. In Section 24-7B, we saw that an amino acid reacts with benzyl chlo-roformate (also called benzyloxycarbonyl chloride) to form a urethane, or carbamate ester, that is easily removed at the end of the synthesis. This protecting group has been used for many years, and it has acquired several names. It is called the benzyloxycarbonyl group, the carbobenzoxy group (Cbz), or simply the Z group (abbreviated Z). 

Reduction of this intermediate by hydrogen transfer from 1,4-cyclohexa-diene in the presence of platinum leads to loss of the carbobenzoxy group and formation of the transient primary amine 119. The terminal primary amino group in that product then participates in a second addition-elimination sequence to form an eight-membered ring (120). Treatment of this intermediate with trimethylsilyl bromide then cleaves the ethyl ethers on phosphorus to give the free phosphonic acid and thus perzinfotel (121). ... 

The X component of the substrate may be derived not only from amino acids but also from alcohols, ammonia, mercaptans, aniline, and p-nitro-phenol. A benzoyl or carbobenzoxy group has generally been employed as the R substituent of the synthetic substrate. Examination of the peptides produced by cleavage of various proteins has confirmed the rather indiscriminate specificity of this group of enzymes. 

Such amides, C6H5CH2OCONHR, differ from most amides, however, in one feature that is significant for peptide synthesis. The carbobenzoxy group can be cleaved by reagents that do not disturb peptide linkages catalytic hydrogenation or hydrolysis with hydrogen bromide in cold acetic acid. 

A comparison of the rates of reaction of many substituted phenyl esters with N-protected a-amino acids showed that the 2,4,5-trichlorophenyl esters are more reactive than p-nitrophenyl esters and are promising new active derivatives for the synthesis of peptides. One advantage is that the ester group does not interfere with catalytic hydrogenation for removal of the carbobenzoxy group. The esters are prepared by condensation of the N-protected amino aeid and the phenol with dicyclo-hexylcarbodiimide. In the synthesis of a particular hexapeptide, where other methods were unsatisfactory because of poor yields or impure products, Bentley et al. obtained the hexapeptide in 97% yield through the trichlorophenyl ester. J. Pless and R. A. Boissonnas, //elr., 46,1609 (1963)... 

Stable for convenient manipulation. For these reasons /-butyl azidoformate is used widely in peptide synthesis. The group is stable to hydrogenation and to sodium in liquid ammonia and is more resistant to alkali than the carbobenzoxy group. It is readily removed by hydrogen bromide in acetic acid. Selective removal of this group in the presence of a carbobenzoxy group can be accomplished with hydrogen chloride in acetic acid, ether, ethyl acetate, or nitromethane. 

Cleavage of N-carbobenzoxy groups Triethylsilane. Trifluoroacetic acid. 

Triethylsilane [1, 1218, before references]. Pettit et at. report a case where cleavage of a carbobenzoxy group with triethylsilane—palladium chloride in the presence of triethylamine proceeded in 70% yield. Hydrogenolysis was effected in somewhat lower yield (60%), and the yield obtained by solvolysis with CF3C02H was only... 

The removal of the carbobenzoxy group has been modified by reductive cleavage using sodium in liquid ammonia or nonhydrolytic cleavage using acidic hydrolysis (HI, HBr or... 

The Era After Emil Fischer. The Carbobenzoxy Group, Max Bergmann and His Scientific Circle... 

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