Blocking groups, in peptide synthesis

Japanese chemists prepare the reagent either by the reaction of acetyl chloride with sodium formate or of formic acid with ketene. The reagent formylates amino acids in formic acid as solvent. The N-formyl group is useful as a blocking group in peptide synthesis. It is surprisingly resistant to basic hydrolysis but readily sol-volyzed in dilute acid. ... 

Blocking group in peptide synthesis. The conversion of an amino acid into its N-formyl derivative does not require preformed acetic-formic anhydride. Sheehan and Yang5 added 83 ml. of acetic anhydride dropwise to a mixture of 0.10 mole of the amino acid in 250 ml. of 88% formic acid at a rate to maintain a temperature of 50-60°. The mixture was stirred at room temperature for 1 hr. and 80 ml. of ice water was added. The mixture was concentrated at reduced pressure and the crystalline residue could be crystallized easily from water or aqueous ethanol. 

The following topics studied in our laboratory will be discussed briefly Synthesis of bracyclic peptides and the potential use of photosensitive blocking groups in peptide synthesis. 

Sheehan and another Nobel laureate Khorana showed independently that the mild carbodiimide mediated synthesis is very useful in the condensation reaction of N-blocked amino acids with a different amino acid to form a peptide bond. The O-blocking of carboxylic acid groups in peptide synthesis with amino nucleophiles, such as glycine esters or amides, " or novel silicon containing protective groups is also mediated by carbodiimides. Likewise, alcohols are protected with 4-benzyloxybutyric acid, using EDC/DMPA. ... 

Block copolymers as solubilizing protecting groups in peptide synthesis were prepared by Bayer et aL [51]. They used 3,5-diisocyanatobenzyl cMoride and 3-nitro-3-azapentane-l,5-diisocyanate as reagents for the syntheris of the copol-ymeric supports ... 

Linear polystyrene can be functionalized by various methods . The functional group capacity in these polymers diould not be too high otherwise, steric complications may arise. Poly(ethylene ycol) has been found to be most suitable for liquid-phase synthesis. This linear polyether and the block copolymers with functional groups at defined distances are chemically stable and soluble in a large number of solvents including water and can be precipitated selectively. Partially hydrolyzed poly(vinylpyrrolidone) and its copolymers with vinyl acetate were successfully applied in peptide synthesis. Poly(acrylic acid), poly(vinyl alcdiol), and poly-(ethylenimine) are less suitable for the sequential type synthesis because of the... 

In peptide synthesis the use of a suitable protection for the N-terminal amino group is required not only to prevent the formation of a complex mixture of oligo- and cyclo-peptides, but an additional demand on the functionality applied for this purpose is that it should prevent possible racemization of the activated amino acid. Racemization usually takes place via an intermediate oxazolone (7) that forms readily from A -acyl-protected amino acids (Scheme 2). This side reaction can be mostly suppressed by using a carbamate as an N-terminal-protecting group. Therefore, nearly all blocking functions currently applied in this field are of the urethane type. 

It is not only benzyl-type urethanes which are widely used for the blocking of amino groups. This goal may also successfully be achieved by the application of alkyl urethanes. Among these, the f-butoxycar-bonyl group (t-BOC or Boc), introduced in 1957, deserves special mention. Today it probably is the most frequently used amino-protecting function in peptide synthesis. The t-BOC group can be easily... 

Hydroxy protection, the temporary protection of the primary and secondary hydroxy functions of Ser and Thr, respectively, and the aromatic hydroxy group of Tyr in peptide synthesis. The blocking of these functionalities is necessary as they can react with acylating reagents. In SPPS, these amino acids are usually protected as benzyl ethers applying Boc/Bzl tactics or as tert.-butyl ethers in Fmoc/Bu chemistry. 

Imidazole protection, temporary protection of the basic and nucleophilic imidazole group of histidine during peptide synthesis. The imidazole moiety has two nonequivalent, but similarly reactive nitrogen atoms, designated tt and r, which cause difficulties in both protection and His racem-ization in peptide synthesis. By application of Boc/Bzl tactics, the jr-benzyloxymethyl (Bom) group is suitable as it prevents racemization and can be cleaved by HE. For Fmoc/Bu chemistry, the best acid-labUe blocking group seems to be r-trityl, as it is stable to bases and cleavable by aqueous TEA at room temperature [T. Brown et al., J. Chem. Soc., Perkin Trans 11982, 1553 P. Sieber, B. Riniker, Tetrahedron Lett. 1987, 28, 6031]. 

Indole protection, temporary blocking of the side-chain group of tryptophan in peptide synthesis. When applying Boc/Bzl tactics, a popular choice for protecting the Trp indole group is the formyl (For) group, as this is removable by treatment with a... 

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