Protecting groups solid phase peptide synthesis

VV Samukov, AN Sabirov, PI Pozdnyakov. 2-(4-Nitrophenyl)sulfonylethoxycarbonyl (Nsc) group as a base-labile a-amino protection for solid phase peptide synthesis. Tetrahedron Lett 35, 7821, 1994. 

The Dde group was developed for amine protection in solid-phase peptide synthesis. It is formed from 2-acetyldimedone in DMF and cleaved using 2% hydrazine in DMF or ethanolamine." Hydrazinolysis of the Dde group in the presence of the... 

Polymer-supported esters are widely used in solid-phase peptide synthesis, and extensive information on this specialized protection is reported annually. Some activated esters that have been used as macrolide precursors and some that have been used in peptide synthesis are also described in this chapter the many activated esters that are used in peptide synthesis are discussed elsewhere. A useful list, with references, of many protected amino acids (e.g., -NH2, COOH, and side-chain-protected compounds) has been compiled/ Some general methods for the preparation of esters are provided at the beginning of this chapter conditions that are unique to a protective group are described with that group/ Some esters that have been used as protective groups are included in Reactivity Chart 6. 

The Bnpeoc group was developed as a base-labile protective group for solid-phase peptide synthesis. The carbamate is formed from the O-succinimide (DMF, 10% Na2C03 or 5% NaHC03) and is cleaved using DBN, DBU, DBU/AcOH, or piperidine. ... 

RE Reid. Solid phase peptide synthesis. A study on the effect of trifluoroacetic acid concentration on the removal of the tert-butyloxycarbonyl protecting group. J Org Chem 41, 1027, 1976. 

BW Erickson, RB Merrifield. Use of chlorinated benzyloxycarbonyl protecting groups to eliminate Ne-branching at lysine during solid-phase peptide synthesis. J Am Chem Soc 95, 3757, 1973. 

K Rosenthal, A Karlstrom, A Unden. The 2,4-dimethylpent-3-yloxycarbonyl (Doc) group as a new nucleophile-resistant protecting group for tyrosine in solid phase peptide synthesis. Tetrahedron Lett 38, 1075, 1997. 

T Vorherr, A Trzeciak, W Bannwart. Application of the allyloxycarbonyl protecting group for the indole of Trp in solid-phase peptide synthesis. Int J Pept Prot Res 48, 553, 1996. 

A Karsltrom, A Unden. A new protecting group for aspartic acid that minimizes piperidine-catalyzed aspartimide formation in Fmoc solid phase peptide synthesis. (3-methylpent-3-yl) Tetrahedron Lett 37, 4234, 1996. 

F Albericio. Orthogonal protecting groups for V-amino and C-terminal carboxyl functions in solid-phase peptide synthesis. Biopolymers (Pept Sci) 55, 123-139, 2000. 

The first version of solid-phase peptide synthesis (SPPS) to be developed used the /-Boc group as the amino-protecting group. It can be cleaved with relatively mild acidic treatment, and TFA is usually used. The original coupling reagent was dicyclohexylcar-... 

The constituent amino acid of dicarba-analogues of cystine is L,L-2,7-diaminosuberic acid [(2S,7S)-2,7-diaminooctanedioic acid, 29, n = 4]. Despite the simplicity of this structure (Scheme 12), the two amino and two carboxy groups must be selectively protected for convenient application in solution and/or solid-phase peptide synthesis. 

The development of chiral peptide-based metal catalysts has also been studied. The group of Gilbertson has synthesized several phosphine-modified amino adds and incorporated two of them into short peptide sequences.[45J,71 They demonstrated the formation of several metal complexes, in particular Rh complexes, and reported their structure as well as their ability to catalyze enantioselectively certain hydrogenation reactions.[481 While the enantioselectivities observed are modest so far, optimization through combinatorial synthesis will probably lead to useful catalysts. The synthesis of the sulfide protected form of both Fmoc- and Boc-dicyclohexylphosphinoserine 49 and -diphenylphosphinoserine 50 has been reported, in addition to diphenylphosphino-L-proline 51 (Scheme 14).[49 To show their compatibility with solid-phase peptide synthesis, they were incorporated into hydrophobic peptides, such as dodecapeptide 53, using the standard Fmoc protocol (Scheme 15).[451 For better results, the phosphine-modified amino acid 50 was coupled as a Fmoc-protected dipeptide 56, rather than the usual Fmoc derivative 52.[471 As an illustrative example, the synthesis of diphe-nylphosphinoserine 52 is depicted in Scheme 16J45 ... 

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