Contemporary Approaches for Amide Bond Formation

Advanced Synthesis & Catalysis, Год журнала: 2023, Номер 365(24), С. 4359 - 4391

Опубликована: Ноя. 7, 2023

Abstract Amide bond construction has garnered significant interest in recent decades due to amides being one of the most prevalent functional groups among bioactive molecules. Out thirty‐seven new drugs approved by FDA 2022, eleven are small molecules containing at least amide bond. Additionally, there nineteen large as drugs, some which have peptide structures, and therefore, also bear bonds. In years, multiple teams embraced challenge developing more efficient methods for formation. This dedication led numerous publications appearing monthly prestigious journals, showcasing advancements this field. The primary goal review is present viable strategies constructing It crucial differentiate between formation synthesis; hence, focus on describing specific forming C(O)−N particular, concentrates developed within last six years. There a particular emphasis approaches that consider thought process when selecting starting materials groups. approach ensures coverage all common chemical transformations yield

Язык: Английский

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Process Mass Intensity (PMI): A Holistic Analysis of Current Peptide Manufacturing Processes Informs Sustainability in Peptide Synthesis

The Journal of Organic Chemistry, Год журнала: 2024, Номер 89(7), С. 4261 - 4282

Опубликована: Март 20, 2024

Small molecule therapeutics represent the majority of FDA-approved drugs. Yet, many attractive targets are poorly tractable by small molecules, generating a need for new therapeutic modalities. Due to their biocompatibility profile and structural versatility, peptide-based possible solution. Additionally, in past two decades, advances peptide design, delivery, formulation, devices have occurred, making peptides an modality. However, manufacturing is often limited solid-phase synthesis (SPPS), liquid phase (LPPS), lesser extent hybrid SPPS/LPPS, with SPPS emerging as predominant platform technology synthesis. involves use excess solvents reagents which negatively impact environment, thus highlighting newer technologies reduce environmental footprint. Herein, fourteen American Chemical Society Green Chemistry Institute Pharmaceutical Roundtable (ACS GCIPR) member companies portfolio compiled Process Mass Intensity (PMI) metrics help inform sustainability efforts This includes PMI assessment on 40 synthetic processes at various development stages pharma, classified according phase. most comprehensive date. The process was divided into (synthesis, purification, isolation) determine respective PMI. On average, (SPPS) (PMI ≈ 13,000) does not compare favorably other modalities such molecules median 168–308) biopharmaceuticals 8300). Thus, high warrants more environmentally friendly manufacturing.

Язык: Английский

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Direct Catalytic Amidations from Carboxylic Acid and Ester Derivatives: A Review

Catalysts, Год журнала: 2023, Номер 13(2), С. 366 - 366

Опубликована: Фев. 7, 2023

The prevalence of amides in biological systems and chemical fields such as polymers, materials natural products drives continuous research on novel procedures to obtain these ubiquitous functional groups. Currently, efforts this purpose are mainly focused around the discovery direct catalytic methods that more atom economic, safe practical for diversified applications (e.g., organic, medicinal peptide chemistries, material polymer purposes, etc.), accordance with green chemistry principles. field amide synthesis has attained a level significance number reviews articles addressing it grown exponentially last decade. Rather than providing general overview amidation methods, which have been described broadly well recent literature, review is highlight formation bonds from amines carboxylic acids or esters. goal emphasize mechanistic aspects, but also discuss substrate tolerance racemization issues (when applicable).

Язык: Английский

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

The Chemical Record, Год журнала: 2023, Номер 23(5)

Опубликована: Март 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.

Язык: Английский

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

The Journal of Organic Chemistry, Год журнала: 2023, Номер 88(14), С. 9853 - 9869

Опубликована: Июль 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.

Язык: Английский

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Cellulase Immobilization on Nanostructured Supports for Biomass Waste Processing

Nanomaterials, Год журнала: 2022, Номер 12(21), С. 3796 - 3796

Опубликована: Окт. 27, 2022

Nanobiocatalysts, i.e., enzymes immobilized on nanostructured supports, received considerable attention because they are potential remedies to overcome shortcomings of traditional biocatalysts, such as low efficiency mass transfer, instability during catalytic reactions, and possible deactivation. In this short review, we will analyze major aspects immobilization cellulase—an enzyme for cellulosic biomass waste processing—on supports. Such supports provide high surface areas, increased loading, a beneficial environment enhance cellulase performance its stability, leading nanobiocatalysts obtaining biofuels value-added chemicals. Here, discuss carbon nanotubes, polymer nanoparticles (NPs), nanohydrogels, nanofibers, silica NPs, hierarchical porous materials, magnetic NPs their nanohybrids, based publications the last five years. The use is especially favorable due easy separation nanobiocatalyst recovery repeated use. This review methods immobilization, morphology multienzyme systems well factors influencing activity achieve highest conversion biowaste into fermentable sugars. We believe allow an enhanced understanding processes, allowing best solutions problems sustainable biorefinery.

Язык: Английский

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Silyl Esters as Reactive Intermediates in Organic Synthesis

Synthesis, Год журнала: 2023, Номер 55(20), С. 3209 - 3238

Опубликована: Апрель 28, 2023

Abstract Silyl esters have been exploited as metastable reaction intermediates, both purposefully and unintentionally, since at least the 1960s. Their reactivity is broadly related to substituents on silicon, in this way their properties can be readily modulated. unique profiles that used generate downstream products of a range functionalities, because many excellent methods for synthesis variety value-added chemicals developed. Furthermore, frequent use hydrosilanes terminal reductants catalytic processes, silyl ester intermediates are likely more commonly utilized by synthetic chemists than currently realized. This review comprehensively summarizes reactions known take advantage reactive discusses examples proceed an unanticipated manner through intermediates. 1 Introduction 2 Synthesis Esters 3 Making Amides from 3.1 Amidation Using Chlorosilanes 3.2 Azasilanes 3.3 Oxysilanes 3.4 Hydrosilanes 3.5 Amine Formation via Amidation/Reduction 3.6 Miscellaneous 4 Mechanistic Investigations 4.1 Mechanism 4.2 4.3 Oxy- or 5 6 Aldehydes, Alcohols, Amines, Alkanes Reduction 6.1 Aldehyde Metal-Free 6.2 Metal-Mediated 6.3 Alcohol 6.4 6.5 Alkane 7 Acid Chlorides 8 In Situ Generated Ramifications Catalysis 9 Conclusion

Язык: Английский

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Organocatalytic Activation of Inert Hydrosilane for Peptide Bond Formation

Organic Letters, Год журнала: 2022, Номер 24(39), С. 7194 - 7199

Опубликована: Сен. 27, 2022

We describe the development of a reliable catalytic protocol for peptide bond formation that is generally applicable to natural and unnatural α-amino acids, β-amino peptides bearing various functional groups. A 10 mol % loading HSi[OCH(CF3)2]3 as catalyst was sufficient guarantee consistently high yield resulting peptide. This method facilitates sustainable utilization resources by using an auxiliary based on earth-abundant silicon.

Язык: Английский

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New nanostructured carriers for cellulase immobilization

Fine Chemical Technologies, Год журнала: 2025, Номер 20(2), С. 119 - 136

Опубликована: Май 6, 2025

Objectives. Cellulase is a multienzyme complex that breaks down cellulose contained in plant cell walls. consists of three types enzymes: endoglucanase, exoglucanase, and β-glucosidase, each which involved the destruction certain chemical bonds cellulose. Nanobiocatalysts based on cellulase immobilized nanostructured carriers are used for catalytic hydrolysis biomass waste, as well food industry environmental protection. This article reviews scientific developments immobilization carriers. Methods. The analyzes papers published over past five years concerned main aspects cellulase, an enzyme processing examines methods immobilization, morphology carriers, factors affecting activity allowing one to achieve maximum conversion cellulose-containing waste origin. Results. Nanostructured have large surface area, providing high efficiency, also create favorable environment activating increasing its stability. allows nanobiocatalysts efficient substrate. conducted analysis latest trends shows positive changes occurred carrier compositions years. describes such graphene layers, polymer nanoparticles, nanohydrogels, nanofibers, silica hierarchical porous materials, magnetic nanoparticles. Conclusions. Magnetically separable increase reliability biocatalyst facilitate biocatalytic processes. use nanoparticles especially advantageous due their easy separation possibility extracting nanobiocatalyst reuse.

Язык: Английский

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

The Journal of Organic Chemistry, Год журнала: 2023, Номер 88(11), С. 6901 - 6910

Опубликована: Май 1, 2023

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

Язык: Английский

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