Carbobenzoxy amino acid

Peptide synthesis. In introducing diphenylketene as a reagent for peptide synthesis, Losse and Demuth" used Staudinger s original synthesis. A carbobenzoxy amino acid is treated with the ketene and the amino acid ester in tetrahydrofurane in the presence of triethylamine. Yields are around 50% optical activity is retained. 

Cleavage of N-carbohenzoxy derivatives. In a general procedure for selective cleavage, the N-carbobenzoxy amino acid or peptide is treated with excess reagent... 

Peptide synthesis. Sheehan and co-workers used this water-soluble reagent for a simplified and rapid synthesis of tetra- and pentapeptides without isolation of intermediates. The reagent (I. I equiv.) is added to a solution of the N-carbobenzoxy-amino acid (I equiv.), the amino acid ester hydrochloride or peptide ester hydrochloride (1 equiv.), and triethylamine (1 equiv.) in methylene chloride. After I hr. at room temperature the solution was washed successively with water (to remove excess reagent and the urea), dilute hydrochloric acid, and sodium bicarbonate solution. The curbobenzoxy group Is removed by hydrogenolysis and the product used directly in the next step. ... 

The reagent is prepared by reaction of silver p-toluenesulfonate with p-nitrobenzyl bromide (88% crude, 80% pure). It reacts with the sodium or trialkylammonium salt of a carbobenzoxy amino acid or peptide in acetone or dimethylformamide to give the p-nitrobenzyl ester in high yield. The protective group is stable to acid and readily removed by catalytic hydrogenation. 

Peptide synthesis. p-Nitrophenol reacts with a carbobenzoxy amino acid in... 

Schistosoma japonicum. The carbobenzoxy (CBz) protected template 160 was initially converted to the a, p-dehydrolactone 161 via the phosphate ester, before undergoing cycloaddition to ylide 162, generated in situ by acidic treatment of A(-benzyl-A(-(methoxymethyl)trimethylsilyl amine. The resultant cycloadduct (163) was isolated in 94% yield as a single diastereoisomer. Destructive template removal, by catalytic hydrogenation, released (5)-( )-cucurbitine, after ion-exchange chromatography, as the free amino acid in 90% yield (Scheme 3.46). 

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

The oxidation of various alcohols by the poly(e-carbobenzoxy-L-lysine)-Cu complex was studied by Welch et aL127. The polymer catalyst showed selectivity in oxidation by virtually excluding alcohols of bulky structure such as diisopropyl and diisobutyl carbinol while admitting simple alcohols arch as n-butyl, iso-butyl, and sec-butyl. It was suggested from structural studies that the selectivity of the polymer catalyst resulted from the highly complex geometry of the molecular cage formed by the helix and the amino acid side chain around the coordinated Cu. The... 

Enantiomers of certain chiral amino acids have been discriminated by using a dedicated potentiometric MIP chemosensor [198]. A sol-gel technique using octa-decyltrichlorosilane in ethanol has been applied for the fabrication of the relevant MIP film. This chemosensor selectively responded to one of the enantiomers of the racemic (N-carbobenzoxy)-(aspartic acid), N-CBZ-Asp, mixture (Fig. 9). The enantiomeric selectivity coefficient was 9 x 10 3 and 4 x 10-3 for the l- and D-enantiomer, respectively. 

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. 

Poly(e-carbobenzoxy-L-lysine)-Cu(II) complex is used in the selective dehydrogenation reaction of alcohol (138,139). X-Ray analysis shows that Cu(II) is coordinated with amide moiety in amino acid residue and peptide moiety in the helix chain, and gives the selectivity in the dehydrogenation (139). 

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). 

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. 

The most commonly used inhibitor is diazoacetylnorleucine methyl ester (DAN) because it allows the determination of the label incorporation by amino acid analysis after complete hydrolysis of the protein. (Abbreviations used are DAN, diazoacetylnorleucine methyl ester EPNP, 1,2-epoxy 3-(nitrophenoxy)propane Z-, carbobenzoxy Phe(NO) >, p-nitrophenylalanyl.) The reaction proceeds as follows ... 

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. 

In (Section 8) we have considered kinetic phenomena encountered during the copolymerization of L- and D-enantiomorphs of a single type of NCA. Copolymerization of mixtures of NCAs of different a-amino acids to give random copolymers is readily realizable [2], one of the earliest examples reported being the synthesis of a DL-phenylalanine L-leucine copolymer by Woodward and Schramm [78]. However, there are few reports on the kinetics of random copolymerization. Shalitin and Katchalski [79] studied the copolymerization of the NCAs of 7-benzyl L-glutamate (A) and e,N-carbobenzoxy L-lysine (B) initiated by diethyl-amine in N,iV-dimethylformamide at 25°C and obtained the interesting result that the over-all rate of reaction (measured by the CO2 evolution) is equal to the sum of the rates of reaction of the individual monomers under similar conditions. The copolymerization is represented schematically in (60)... 

Carbobenzoxy (Cbo) and /m-butyloxycarbonyl (BOC) amino acids are very useful in the synthesis of peptides and, consequently, their separation from each other and from unreacted components used in their preparation is very important. 

A stable solid, this reagent gives derivatives of amino acids and peptides that are higher melting and better crystalline than the carbobenzoxy derivatives. ... 

The reagents are used for making mixed anhydrides that serve as intermediates in peptide synthesis." A protected amino acid, such as the N-carbobenzoxy derivative (Cb), is brought into solution in toluene or tetrahydrofurane by addition of enough tiiethylamine to form the salt and a butyl chloroformate is added at 0°... 

Khorhna" used DCC for the preparation of symmetrical anhydrides of N-protected amino acids. Thus when N-carbobenzoxy-DL-phenylalanine was stirred at room temperature in ether with DCC the anhydride precipitated along with... 

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)... 

Formation of the IV-carbobenzoxy derivative of an amino acid for use in peptide synthesis and liberation of the amino group at an appropriate stage of synthesis by hydrogenolysis of the activated CO bond. 

Yields of 65-90% are obtained on a 50 g scale for fourteen different amino acids. Cleavage of benzyl and carbobenzoxy groups1- is also possible. 

M8. Maskaleris, M. L., Sevendal, E. S., and Kibrick, A. C., Carbobenzoxy derivatives of amino acids and peptides Instant thin-layer chromatography as hydrobromides. J. Chromalog. 23, 403-409 (1966). 

Z, or a carbobenzoxy (benzyloxycarbonyl) group (amino acid and peptide chemistry) Cbz... 

The reaction of phosgene with benzyl alcohol yields benzyl chloroformate (carbobenzoxy chloride), CICO2CH2C6H5, useful in protecting (Ege, 1999) amino groups of amino acids. (Deprotection is accomplished with H2/Pd/C.)... 

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