2-Methoxy-4-methylsulfinylbenzyl Alcohol as a Safety-Catch Linker for the Fmoc/<i>t</i>Bu Solid-Phase Peptide Synthesis Strategy

Nandhini, K. P.; Alberício, Fernando; Torre, Beatriz G. de la

doi:10.1021/acs.joc.2c01057

Cited by 5 publications

(6 citation statements)

References 46 publications

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“…Me3SiCl + 10 eq. Ph3P, (3 × 1 h) in THF [13,65] Various naturally existing peptides, particularly hormones like oxytocin, secretin, and calcitonin, possess a C-terminal amide function. As a result, Patek and Lebl [63,66] developed safety-catch amide-anchor groups that could be removed using TFA-based methods at the end.…”

Section: The Reductive-acidolytic Safety-catch Linkersmentioning

confidence: 99%

“…In contrast, under reductive acidolysis with SiCl4-thioanisole-anisole-TFA for 3 h, 94% of Leu was successfully cleaved from the resin [58]. Likewise, Undén and Erlandsson [57] Our group introduced the Mmsb linker [13], which is compatible with both Boc and Fmoc chemistry SPPS. Peptide-O-Mmsb-resin was synthesized, and the linker exhibited stability to the treatments, with piperidine and TFA used for the removal of Fmoc and Boc protecting groups, respectively.…”

Section: The Reductive-acidolytic Safety-catch Linkersmentioning

confidence: 99%

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Safety-Catch Linkers for Solid-Phase Peptide Synthesis

Noki,

de la Torre,

Albericio

2024

Molecules

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Solid-phase peptide synthesis (SPPS) is the preferred strategy for synthesizing most peptides for research purposes and on a multi-kilogram scale. One key to the success of SPPS is the continual evolution and improvement of the original method proposed by Merrifield. Over the years, this approach has been enhanced with the introduction of new solid supports, protecting groups for amino acids, coupling reagents, and other tools. One of these improvements is the use of the so-called “safety-catch” linkers/resins. The linker is understood as the moiety that links the peptide to the solid support and protects the C-terminal carboxylic group. The “safety-catch” concept relies on linkers that are totally stable under the conditions needed for both α-amino and side-chain deprotection that, at the end of synthesis, can be made labile to one of those conditions by a simple chemical reaction (e.g., an alkylation). This unique characteristic enables the simultaneous use of two primary protecting strategies: tert-butoxycarbonyl (Boc) and fluorenylmethoxycarbonyl (Fmoc). Ultimately, at the end of synthesis, either acids (which are incompatible with Boc) or bases (which are incompatible with Fmoc) can be employed to cleave the peptide from the resin. This review focuses on the most significant “safety-catch” linkers.

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Section: The Reductive-acidolytic Safety-catch Linkersmentioning

confidence: 99%

Section: The Reductive-acidolytic Safety-catch Linkersmentioning

confidence: 99%

Safety-Catch Linkers for Solid-Phase Peptide Synthesis

Noki,

de la Torre,

Albericio

2024

Molecules

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“…In the work by our group, 31 however, we developed a highly efficient two-step solid-phase procedure for the cleavage of a linker with a structure similar to those of the protecting groups reported herein. It involves three consecutive treatments with Me 3 SiCl/Ph 3 P (20:10 equiv) in THF for 1 h, washing the sample twice with THF between treatments, and washing the peptide resin successively with THF, DCM, DMF, and DCM.…”

Section: Preparation Of Model Peptides Containing Msib and Msbh As Th...mentioning

confidence: 99%

Solid-Phase Peptide Synthesis Using a Four-Dimensional (Safety-Catch) Protecting Group Scheme

Noki

Brasil

Zhang³

et al. 2022

J. Org. Chem.

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Peptides of importance to both academia and industry are mostly synthesized in the solid-phase mode using a two-dimensional scheme. The so-called Fmoc/tBu strategy, where the groups are removed by piperidine and TFA, respectively, is currently the method of choice for peptide synthesis. However, as the molecular diversity of cyclic and branched peptides becomes a challenging interest, a high level of orthogonal dimensionality is required, such as through triorthogonal protection schemes. Here we present a fourth category of orthogonal protecting groups that are stable under cleavage conditions, including the TFA treatment that removes the tBu-based groups. At the end of the synthetic process and upon some chemical manipulation, the groups in this fourth category were removed with TFA. This new concept of protecting groups could facilitate the synthesis and manipulation of difficult peptides.

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“…2). Furthermore, the Mmsb/Mmtb linker and other related linkers has been used by several groups in N α -Boc strategies 16–18 and by our group as semipermanent protecting group in a N α -Fmoc strategy. 19…”

Section: Introductionmentioning

confidence: 99%

“…2). Furthermore, the Mmsb/Mmtb linker and other related linkers has been used by several groups in N α -Boc strategies [16][17][18] and by our group as semipermanent protecting group in a N α -Fmoc strategy. 19 The above described safety-catch protecting groups and linker are fully stable to acid and base conditions and are thus compatible with Fmoc and Boc chemistry.…”

Section: Introductionmentioning

confidence: 99%