Protecting groups in peptide synthesis

W Kessler, B Iselin. Selective deprotection of substituted phenylsulfenyl protecting groups in peptide synthesis. Helv Chim Acta 49, 1330, 1966. 

GM Anantharamaiah, KM Sivanandaiah. Transfer hydrogenation. A convenient method for the removal of commonly used protecting groups in peptide synthesis, (formic acid) J Chem Soc Perk Trans 1 490, 1977. 

H Yajima, Y Kiso, H Ogawa, N Fujii, H Me. Studies on peptides. L. Acidolysis of protecting groups in peptide synthesis by fluorosulphonic acid and methanesulfonic acid. Chem Pharm Bull (Jpn) 23, 1164, 1975. 

DA Pearson, M Blanchette, ML Baker, CA Guindon. Trialkylsilanes as scavengers for the trifluoroacetic acid deblocking of protecting groups in peptide synthesis. Tetrahedron Lett 30, 2739, 1989. 

The addition of hydrazine to diphenylvinylene carbonate 92 quantitatively affords a 1 1 mixture of perhydro-l,3,4-oxadiazin-2-one 93 and 2-oxazolidinone 94 derivatives, both of which are smoothly dehydrated with P2O5 to afford 1,3,4-oxadiazin-2-one 95 and 3-amino-2(3//)-oxazolone 96 (Fig. 5.24), respectively. Addition of primary amines to diphenylvinylene carbonate results in exclusive formation of 3-aIkyl-2(3//)-oxazolones, previously investigated as amino protecting groups in peptide synthesis. 

The adamantyloxycarbonyl function has also been found to be a useful protecting group in peptide synthesis 209 The general reaction sequence is summarized in Scheme 19. The success of this peptide synthesis perhaps results from the bulk of the adamantyl group which directs attack to the desired carbonyl group. 

Co and Cr ammines were among the first to be investigated by Reinecke, Jmgensen, Werner (Nobel prize, 1912), and Pfeiffer in the early days of coordination chemistry see Coordination Chemistry History), and this work continues today (Taube, Nobel Prize, 1984). [MX(NH3)5]"+ (X = anionic or neutral group) is particularly well-studied and has even been used as a protecting group in peptide synthesis. Variation of M has a considerable influence on the rate of the Solvolysis of X (Table 4). 

Removal of protective groups in peptide synthesis. The reagent, dis.solved in tri-fluoroacetiu acid, removes various acid-Iabiie N-protecting groups (Cb, BOC, etc.) at 0°. It also removes nitro, tosyl, or p-methoxybenzyl groups used for protection of side-chain groups. 

Allyl (Al) esters are suitable for the temporary protection of carboxy groups in peptide and glycopeptide synthesisP " and also in the synthesis of cyclic peptides.In the latter case these esters allow, for example, on-resin head-to-taU cyclizations of peptides that are attached via the side chains of aspartic acid and glutannic acid residues to the solid support.t 1 The application of aUylic protecting groups in peptide synthesis has been comprehensively reviewed by Guibe.f ... 

The use of enzymes for cleaving protecting groups in peptide synthesis has been re-viewedf " and is described in Section 2.5.3. 

Azidoformates are used mainly for two purposes the generation of alkoxycarbonylnitrenes (see section ILF) and the introduction of alkoxycarbonyl protecting groups in peptide synthesis (see section II.C). 

Di -re/ -butyl-4-oxo-l-phenyl-2,5-cyclohexadiene may be used as a protecting group in peptide synthesis it can be introduced by electrochemical oxidation [178,179] ... 

Temporary protecting group in peptide synthesis. Provides an aromatic binding site for some enzymes. Chemical symbol CBZ... 

Figure 18.2 N -Amino protecting groups in peptide synthesis.

Since the ribosomal peptidyltransferase activity is not suitable for practical use as a simple C - N ligase and, in addition, the multienzyme complexes involved in bacterial peptide synthesis[S] do not seem to possess a general applicability, only the reverse catalytic potential of peptidases can be considered as valuable supplement to chemical coupling methods (cf. Sect. 12.5.3). In addition, peptidases have been used successfully for enzymatic manipulation of protecting groups in peptide synthesis 7-9 . 

Cbz The phenyl met box ycarbonyl group, a protecting group in peptide. synthesis. Cellulose A poly.saccharide of glucose linked at C-4. 

Boc The I,l-dimethyleihyoxycarbonyl group, a protecting group in peptide. synthesis. 

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