Game Change from Reagent- to Substrate-Controlled Peptide Synthesis

Bulletin of the Chemical Society of Japan, Journal Year: 2020, Volume and Issue: 93(6), P. 759 - 767

Published: March 31, 2020

Abstract An account of the development Lewis-acid-catalyzed methods for racemization-free peptide synthesis is presented. These are based on substrate control concept that has been exploited extensively in stereoselective reactions, but never previously applied to synthesis. The most important difference emerged between our and conventional reagent such as coupling-reagent-mediated boronic-acid-catalyzed bond-forming reactions how activate reaction sites racemization control. reagent-controlled proceed by generating highly reactive esters situ, leading occasional through formation oxazolone intermediates. On other hand, substrate-controlled do not go known processes because Lewis acids we use herein designed moderately an anchor a specific carbonyl group located at reasonable distance from directing group. Based concept, have developed six novel methodologies over last five years.

Language: Английский

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Diboronic Acid Anhydride-Catalyzed Direct Peptide Bond Formation Enabled by Hydroxy-Directed Dehydrative Condensation

Organic Letters, Journal Year: 2020, Volume and Issue: 22(21), P. 8658 - 8664

Published: Oct. 12, 2020

We report the catalytic direct peptide bond formations via dehydrative condensation of β-hydroxy-α-amino acids, affording serine, threonine, or β-hydroxyvaline-derived peptides in high to excellent yields with functional group tolerance, minimum epimerization, and chemoselectivity. The key success these atom-economical transformations is use diboronic acid anhydride catalyst for hydroxy-directed reactions.

Language: Английский

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Selective breakage of C H bonds in the key oxidation intermediates of gaseous formaldehyde on self-doped CaSn(OH)6 cubes for safe and efficient photocatalysis

Applied Catalysis B Environment and Energy, Journal Year: 2020, Volume and Issue: 277, P. 119214 - 119214

Published: June 9, 2020

Language: Английский

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Biphasic electrochemical peptide synthesis

Chemical Science, Journal Year: 2021, Volume and Issue: 12(39), P. 12911 - 12917

Published: Jan. 1, 2021

The large amount of waste derived from coupling reagents is a serious drawback peptide synthesis green chemistry viewpoint. To overcome this issue, we report an electrochemical in biphasic system. Anodic oxidation triphenylphosphine (Ph3P) generates phosphine radical cation, which serves as the reagent to activate carboxylic acids, and produces oxide (Ph3P[double bond, length m-dash]O) stoichiometric byproduct. In combination with soluble tag-assisted liquid-phase synthesis, selective recovery desired peptides Ph3P[double m-dash]O was achieved. Given that methods reduce Ph3P have been reported, could be recyclable byproduct unlike byproducts typical reagents. Moreover, commercial active pharmaceutical ingredient (API), leuprorelin, successfully synthesized without use traditional

Language: Английский

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Amide bond formation: beyond the dilemma between activation and racemisation

Chemical Communications, Journal Year: 2021, Volume and Issue: 57(52), P. 6346 - 6359

Published: Jan. 1, 2021

The development of methods for amide bond formation without recourse to typical condensation reagents has become an emerging research area and been actively explored in the past quarter century.

Language: Английский

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Methyltrimethoxysilane (MTM) as a Reagent for Direct Amidation of Carboxylic Acids

Organic Letters, Journal Year: 2022, Volume and Issue: 24(5), P. 1175 - 1179

Published: Jan. 27, 2022

Methyltrimethoxysilane [MTM, CH3Si(OMe)3] has been demonstrated to be an effective, inexpensive, and safe reagent for the direct amidation of carboxylic acids with amines. Two simple workup procedures that provide pure amide product without need further purification have developed. The first employs aqueous base-mediated annihilation MTM. second involves crystallization from reaction mixture providing a low process mass intensity protocol.

Language: Английский

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Less Is More: N(BOH)₂ Configuration Exhibits Higher Reactivity than the B₃NO₂ Heterocycle in Catalytic Dehydrative Amide Formation

Organic Letters, Journal Year: 2023, Volume and Issue: 25(4), P. 694 - 697

Published: Jan. 20, 2023

Diboron substructures have emerged as a promising scaffold for the catalytic dehydrative amidation of carboxylic acids and amines. This Letter describes design, synthesis, evaluation first isolable N(BOH)2 compound an catalyst. The new catalyst outperforms previously reported B3NO2 heterocycle catalyst, with respect to turnover frequency, albeit former gradually decomposes upon exposure work opens up avenue designing better direct amidation.

Language: Английский

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DMAPO/Boc₂O‐Mediated One‐Pot Direct N‐Acylation of Less Nucleophilic N‐Heterocycles with Carboxylic Acids

ChemCatChem, Journal Year: 2023, Volume and Issue: 15(5)

Published: Jan. 13, 2023

Abstract In contrast to the considerable progress in development of methodologies for amide bond formation amines, direct N ‐acylation less nucleophilic ‐heterocycles and amides with carboxylic acids is still challenging. this report, we describe heterocycles promoted by 4‐( , ‐dimethylamino)pyridine ‐oxide (DMAPO)/di‐ tert ‐butyl dicarbonate (Boc 2 O) system. The new one‐pot method, which does not involve pre‐activation substrates, enables a wide variety nitrogen nucleophiles such as indole, carbazole, pyrrole, pyrazole, lactam, oxazolidinone, anilide high yield. method also exhibits excellent functional group tolerance broad substrate scope. As present practical, operationally simple, scalable, it should find applications both academic industrial laboratories.

Language: Английский

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Recent Advances in Carbon‐Nitrogen/Carbon‐Oxygen Bond Formation Under Transition‐Metal‐Free Conditions

The Chemical Record, Journal Year: 2023, Volume and Issue: 23(5)

Published: March 30, 2023

Carbon-heteroatom bond formation under transition-metal free conditions provides a powerful synthetic alternative for the efficient synthesis of valuable molecules. In particular, C-N and C-O bonds are two important types carbon-heteroatom bonds. Thus, continuous efforts have been deployed to develop novel C-N/C-O methodologies involving various catalysts or promoters TM-free conditions, which enables functional molecules comprising in facile sustainable manner. Considering significance construction organic materials science, this review aims comprehensively present selected examples on (including amination amidation) etherification hydroxylation) without transition metals. Besides, involved promoters/catalysts, substrate scope, potential application possible reaction mechanisms also systematically discussed.

Language: Английский

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On the Use of Triarylsilanols as Catalysts for Direct Amidation of Carboxylic Acids

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(14), P. 9853 - 9869

Published: July 11, 2023

Triarylsilanols have been reported as the first silicon-centered molecular catalysts for direct amidation of carboxylic acids with amines identified after a screen silanols, silanediols, disiloxanediols, and incompletely condensed silsesquioxanes potential homogeneous catalysts. Subsequent synthesis testing various electronically differentiated triarylsilanols tris(p-haloaryl)silanols more active than parent triarylsilanol, where bromide congener is found to be most active. Catalyst decomposition can observed by NMR methods, but RPKA methods reveal that product inhibition operative, tertiary amides are inhibitory secondary amides. Studies using an authentically synthesized triaryl silylester putative intermediate in catalytic system enable plausible mechanism proposed supported computationals.

Language: Английский

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