Peptide synthesis by a combination of solid-phase and solution methods III resin derivatives allowing minimum-racemization coupling of nα-protected amino acids

Mergler, M.; Nyfeler, R.; Gosteli, J.

doi:10.1016/s0040-4039(00)70665-4

Cited by 24 publications

(9 citation statements)

References 9 publications

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“…One of the earliest described examples of preparation of pyrrolidines on solid support was reported by Hollinshead [156], who developed a solid-phase protocol for the preparation of highly functionalized pyrrolidines based on the reaction of azomethine ylides with polymer-bound a,b-unsaturated ketones. Thus, chlorinated Wang resin 110 [157] is coupled to 3-hydroxyacetophenone 111 with Cs 2 CO 3 /NaI in DMF, affording acetophenone tethered to the solid support (112). Knoevenagel condensation with different aromatic aldehydes using a 0.5 M solution of MeONa/MeOH affords the corresponding enones 113.…”

Section: Synthesis Of Pyrrolidinesmentioning

confidence: 99%

Solid Phase and Combinatorial Chemistry in the Heterocyclic Field

Villalgordo¹

2011

Modern Heterocyclic Chemistry

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Section: Synthesis Of Pyrrolidinesmentioning

confidence: 99%

Solid Phase and Combinatorial Chemistry in the Heterocyclic Field

Villalgordo¹

2011

Modern Heterocyclic Chemistry

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“…The most frequently used method for ester formation is esterification of resin-bound hydroxy linkers with N-protected amino acids. Alternatively, nucleophillic substitution of benzyl derivatives substituted by chloro [48][49][50][51], bromo [51,52], mesyl [50,52], tosyl [52], diazo [53], and trichloroacetimidate [54] groups have been used for ester formation.…”

Section: Estersmentioning

confidence: 99%

Linkers for Solid‐Phase Peptide Synthesis

Soural

Hlaváč

Krchňák

2010

Amino Acids, Peptides and Proteins in Organic Chemistry

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“…The most widely used polymeric supports are the chlorotrityl chloride (CTC, Barlos) resin [8][9][10], followed by SASRIN (super acidsensitive resin) resin [11][12][13][14], and the p-methylbenzhydrylbromide (bromide) resin ( Figure 10.3) [15]. For the preparation of a C-terminal peptide acid, there are three commercially available resins, which are broadly used and are labile to a low concentration of TFA.…”

Section: Cleavagementioning

confidence: 99%

“…A 1-2% TFA concentration is recommended for SASRIN resin [11][12][13][14]. A 1-2% TFA concentration is recommended for SASRIN resin [11][12][13][14].…”

Section: Cleavagementioning

confidence: 99%

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Fmoc Methodology: Cleavage from the Resin and Final Deprotection

Alberício

Tulla‐Puche

Kates³

2010

Amino Acids, Peptides and Proteins in Organic Chemistry

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The fluorenylmethoxycarbonyl (Fmoc)/tert-butyl (tBu) solid-phase method is categorically the present strategy of choice for the preparation of peptides for both research and industrial scales [1][2][3][4][5]. The main advantage of the Fmoc/tBu approach compared to the earlier tert-butyloxycarbonyl (Boc)/benzyl (Bzl) strategy is the conditions used to remove the temporal protecting group (Fmoc) and the permanent side-chain protecting groups as well as the separation/cleavage of the peptide from the resin. For the Boc/Bzl strategy, each removal of the temporal protecting group (Boc) requires treatment with trifluoroacetic acid (TFA) and the final stepthe cleavage of the peptide from the resinideally requires the concourse of HF. Although HF provokes very clean chemical reactions and is an optimal reagent to incorporate into a synthetic strategy, its use requires special Teflon reservoirs and may be forbidden in some geographical areas by local safety departments. These drawbacks are further magnified at an industrial scale. Conversely, the Fmoc/tBu strategy requires typically one or a maximum of two acid treatments.The absence of TFA for the release of the temporal protecting group in the Fmoc/ tBu strategy allows a gradual removal/cleavage of the remaining protecting groups. A final treatment of the peptide resin with a high concentration of TFA (approximately 90%) will render the totally free unprotected peptide. Alternatively, after choosing the proper resin, it is possible first to remove the protected peptide from the resin (1-5% TFA) and then to obtain the free peptide by treatment with a high concentration of TFA (Figure 10.1). This two-step cleavage/deprotection strategy allows modulation of the TFA treatment to minimize side-reactions and therefore increase the quality of the final product.Conversely, the protected peptide may be further elongated in solution by reaction with other protected peptides also prepared by solid-phase to accomplish the target molecule (convergent strategy, Figure 10.2) [6,7].Although there has been continuous development of new resins, linkers, protecting groups, and coupling reagents (see Chapter 12), the treatment of the protected peptide(-resin) with a high concentration of TFA is perhaps the key step for obtaining

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Peptide synthesis by a combination of solid-phase and solution methods III resin derivatives allowing minimum-racemization coupling of nα-protected amino acids

Cited by 24 publications

References 9 publications

Solid Phase and Combinatorial Chemistry in the Heterocyclic Field

Solid Phase and Combinatorial Chemistry in the Heterocyclic Field

Linkers for Solid‐Phase Peptide Synthesis

Fmoc Methodology: Cleavage from the Resin and Final Deprotection

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