An economical approach for peptide synthesis<i>via</i>regioselective C–N bond cleavage of lactams

Muramatsu, Wataru; Yamamoto, Hisashi

doi:10.1039/d2sc01466a

Cited by 3 publications

(4 citation statements)

References 104 publications

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“…10a b Our research group has recently introduced DKPs as crucial constituents in peptide elongation. 10c It is noteworthy that DKP-based peptide synthesis follows an ‘amide-to-amide’ transformation, necessitating the targeted activation of one of the amide NH groups in DKPs using an appropriate protective group. 10 This study demonstrates the straightforward method for the synthesis of mono-Boc-DKPs and their potency as activated substrates for amide substitution in DKPs, leading to the formation of peptide bonds.…”

Section: Table 1 Optimization Of Reaction Conditions Fo...mentioning

confidence: 99%

“…10 Conventionally, the synthesis of mono-Boc-protected DKPs composed of the same amino acids (symmetrical DKPs) can be achieved by deprotecting one of the Boc functionalities in bis-Boc-protected DKP using one equivalent of TFA. 10c However, this method necessitates a two-step process, resulting in a mixed product and low yields of the desired mono-Boc-protected DKP (Scheme 1c ). To the best of our knowledge to date, no protocol has been established for the regioselective protection of one of the amide NH groups in DKPs constructed using different amino acids (unsymmetrical DKPs).…”

Section: Table 1 Optimization Of Reaction Conditions Fo...mentioning

confidence: 99%

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Triisobutylaluminium-Mediated Regioselective Protection of Sterically Hindered Amide NH of Cyclo-(AA-Gly): Key Building Block for Next-Generation Peptide Synthesis

Ramakrishna,

Hattori,

Yamamoto

et al. 2023

Synlett

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In this study, we address the challenge of regioselective Boc protection in the more sterically hindered amide NH of unsymmetrical 2,5-diketopiperazines (DKPs) formed from glycine and various amino acids. Our research introduces a novel technique utilizing cost-effective triisobutylaluminium and trimethoxysilane. Notably, trimethoxysilane selectively reacts with the less hindered amide NH, facilitating the regioselective Boc protection of the more congested amide NH in DKPs. The primary objective of our work is to develop a straightforward and scalable approach for the synthesis of Boc-protected DKPs, with a focus on addressing the steric challenges presented by these compounds. We successfully demonstrate the scalability of this method, enabling the synthesis of a variety of mono-Fmoc, Cbz, Alloc, and EtOCO-protected DKPs. Furthermore, we extend the applicability of this strategy by employing it in the construction of pentapeptides through a twofold-peptide elongation process. Our findings reveal the versatility and efficiency of this regioselective Boc protection method. Overall, this research introduces a valuable solution to the regioselective Boc protection challenge in DKPs and demonstrates its applicability in peptide synthesis, showcasing its potential for further advancements in the field.

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Section: Table 1 Optimization Of Reaction Conditions Fo...mentioning

confidence: 99%

Section: Table 1 Optimization Of Reaction Conditions Fo...mentioning

confidence: 99%

Triisobutylaluminium-Mediated Regioselective Protection of Sterically Hindered Amide NH of Cyclo-(AA-Gly): Key Building Block for Next-Generation Peptide Synthesis

Ramakrishna,

Hattori,

Yamamoto

et al. 2023

Synlett

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“…Diketopiperazines (DKPs) are the smallest cyclic peptides consisting of two amino acids and important privileged structures in many natural products and bioactive molecules. , Their conformationally constrained heterocyclic dimensions are valuable for designing new classes of pharmaceuticals, materials, − and synthetic scaffolds . A unique DKP structure containing a hydroxymethyl functional group is often found in many natural products, such as chaetocin, hyalodendrin, gliotoxin, gliovictin, ,, and (+)-T-988A–C .…”

Section: Introductionmentioning

confidence: 99%

Concise Synthesis of 2,5-Diketopiperazines via Catalytic Hydroxy-Directed Peptide Bond Formations

et al. 2023

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2,5-Diketopiperazines (DKPs) with hydroxymethyl functional groups are essential structures found in many bioactive molecules and functional materials. We have established a simple protocol for the concise synthesis of this type of DKPs through diboronic acid anhydride-catalyzed hydroxy-directed peptide bond formations. The sequential reactions in this report, which consist of three steps, an intermolecular catalytic condensation reaction in which water is the only byproduct, a simple deprotection of the nitrogen-protecting group, and an intramolecular cyclization, enabled the synthesis of functionalized DKPs in high to excellent yields without any intermediate purification. The utility of this protocol has been demonstrated by synthesizing natural products, phomamide and Cyclo(Deala-L-Leu).

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“…Biologically active peptides may be natural compounds of food or part of protein that are inactive in the precursor molecule. Because peptides are synthesized by focusing on developing general condensation agents, ensuring low risk of racemization issues like health hazards, waste generation and atom economy have abonded they are being extensively exploited in pharmaceuticals and cosmetics, by repeating a condensation-agent-mediated amidation followed by deprotection the peptides are synthesised [2]. After enzymatic cleavage with selective heat-induced precipitation of (Glutathione-S-transferase) GST-affinity tag the peptides are purified.…”

Section: Introductionmentioning

confidence: 99%

A Review on Peptide Synthesis: Therapeutic agents, stabilizing agents and its applications

T¹,

Khaleel²,

Ramesh³

et al. 2023

J Integral Sci

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Peptides are required as a part of health through their extended activity. Peptides are also purified because of their high target affinity. The synthesis includes both the conventional method and the microwave method among which microwave procedure is considered superior due to less reaction time and higher yeilds. The peptides were assessed for the inhibition activity of Urokinase plasminogen (UpA), coagulation factor XII, and also for the cytotoxicity and anti-microbial activity.

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An economical approach for peptide synthesisviaregioselective C–N bond cleavage of lactams

Abstract: An economical, solvent-free, and metal-free method for peptide synthesis via C–N bond cleavage using lactams has been developed. The method not only eliminates the need for condensation agents and their...

Cited by 3 publications

References 104 publications

Triisobutylaluminium-Mediated Regioselective Protection of Sterically Hindered Amide NH of Cyclo-(AA-Gly): Key Building Block for Next-Generation Peptide Synthesis

Triisobutylaluminium-Mediated Regioselective Protection of Sterically Hindered Amide NH of Cyclo-(AA-Gly): Key Building Block for Next-Generation Peptide Synthesis

Concise Synthesis of 2,5-Diketopiperazines via Catalytic Hydroxy-Directed Peptide Bond Formations

A Review on Peptide Synthesis: Therapeutic agents, stabilizing agents and its applications

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