Carbobenzoxy method

Problem 21.49 Prepare glycylalanyltyrosine from the free amino acids by the carbobenzoxy method. ... 

Bergmann Azlactone Peptide Synthesis Bergmann Degradation Bergmann-Zervas Carbobenzoxy Method Bergs (see Bucherer-Bergs Reaction)... 

Zervas (see Bergmann-Zervas Carbobenzoxy Method) Ziegler (see Thorpe-Ziegler Method)... 

The new era in the development of peptide S3mthesis began with the so-called carbobenzoxy method of Bergmann-Zervas (2). Thirty five years after its introduction the carbobenzoxy method is still the method of choice, especially since Bergmann and Zervas (3) have adapted it to almost all the known amino acids and du Vigneaud ( ) to S-benzyl cysteine. These procedures made possible the sjmthesis (1) of thousands of peptides and of peptide hormones e.g. oxytocin (du Vigneaud), ACTH (Schwyzer), insulin (Katsoyannis, Zahn, Du). 

In many cases it is possible to use at first the carbobenzoxy method for the synthesis of a peptide, and then to exchange the amino-protecting group for the trityl or the NPS-group, so that the synthesis can be continued on a new basis. This possibility was pointed out in our laboratory long ago(6), and has in the meantime been applied successfully by Schwyzer(17) and by Zahn(18). 

Nach der gleichen Methode wurde die d -Glucosaminuronsdure dargestellt (93). iV-Carbobenzoxy-a-bcnzylglucosaminid lieferte durch... 

Benzyl chloroformate has been prepared by action of phosgene on benzyl alcohol.1 2 The methods described here for the preparation of benzyl chloroformate and the carbobenzoxy deriva-... 

Besides the hydrosilylation already described (vide supra), silanes are able to hydrogenate a great variety of substrates. Since the early 1960 s a common method in the peptide chemistry is the cleavage of the carbobenzoxy(cbo)protection group via Et3SiH (i20)/PdCl283 which enables the amino acid to be obtained in a one step reaction (Scheme 14) ... 

The peptides 3 were prepared by condensation of phtaloyl,N-carbobenzoxy,N-t-butoxycarbonyl or N-fomyl-amino acids with 1-aminoalkanephosphonic acids as well as with their dialkyl or diphenyl esters /Scheme/. Special attention was payed on theefectiveness of the peptide bond formation and on the methods for selective and total removal of the blocking groups. 

N-Acylsaccharins (13) possess a certain potential as acylating agents. They will acylate amines, but will react with water or alcohols only when acid or base is present.167 The method was used to acylate a-amino-penicillanic acid.170 Micheel162-165 has based a peptide (38) synthesis on the acyl transfer from 31 [Z = carbobenzoxy, obtained through reaction with DCC or with pseudosaccharin chloride (6) or with thionyl chloride and imidazole] to amino acids. Pseudosaccharin anhydride 323, lee js thg product of a condensation between 6 and 1, mostly from hydrolysis of 6. Formation of 32 tends to occur in nonprotic solvents with base catalysis, even when practical precautions are taken to exclude moisture. Water and protic solvents seem to shield the anion 19 and prevent attack on 6. 

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)... 

Hydrazides —> Azides. The acid azide method of peptide synthesis, for example of the protected dipeptide (3), has the advantage that no racemization of the peptide vomptments occurs. However, conversion of N-carbobenzoxy-S-benzyl-u-cysteine hydni/.lde (I) into the azide by reaction with nitrous acid under normal conditions (ITor ls considerable amide as by-product (Rt ONHNHNO — RCONH> + fiBaNHaOl. Amide formation can be lUDoraiiad hv onaratlna at hlah aoiditv and... 

Other methods for effecting the removal of the carbobenzoxy group that have found use in polypeptide synthesis include reduction by sodium in liquid ammonia and treatment with concentrated HBr. ... 

High molecular-weight polypeptides were synthesized by the standard N-carboxy-o-amino acid anhydride (NCA) method. The u-carbobenzoxy groups of the polypeptide in dioxane solution were removed with hydrogen bromide gas. The water-soluble polymers were then dialyzed repeatedly against dilute HCl and finally water. The concentrations of the polypeptides were determined by microKjeldahl analyses. All CD spectra were measured on a Jasco J-10 or, more recently, J-500A spectropolarimeter (for its calibration, see Ref. 8). 

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