Large-Scale Amidations in Process Chemistry: Practical Considerations for Reagent Selection and Reaction Execution

Organic Process Research & Development, Journal Year: 2022, Volume and Issue: 26(6), P. 1562 - 1689

Published: June 7, 2022

This review describes the practical aspects involved in implementation of large-scale amidations process chemistry. Coupling reagent, base, additive, and solvent selections are critically analyzed to highlight their pros cons. Other important factors be considered on large scale, such as atom economy, cost, safety, toxicity, also examined. These concepts then showcased through selected examples from literature for synthesis active pharmaceutical ingredients.

Language: Английский

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Biocatalytic amide bond formation

Green Chemistry, Journal Year: 2023, Volume and Issue: 25(8), P. 2958 - 2970

Published: Jan. 1, 2023

The state-of-the-art of biocatalytic amide bond formation is discussed with the help a manually curated database enzymatic amidation reactions.

Language: Английский

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Contemporary Approaches for Amide Bond Formation

Advanced Synthesis & Catalysis, Journal Year: 2023, Volume and Issue: 365(24), P. 4359 - 4391

Published: Nov. 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

Language: 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, Journal Year: 2024, Volume and Issue: 89(7), P. 4261 - 4282

Published: March 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.

Language: Английский

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Electrocatalytic C−N Couplings at Cathode and Anode

Advanced Energy Materials, Journal Year: 2024, Volume and Issue: 14(28)

Published: Feb. 21, 2024

Abstract Electrocatalytic C−N couplings are promising alternatives to construct bonds and synthesize vital chemicals, including amine, amide, amino acid, oxime, imine, nitrile, under ambient conditions. In recent years, the electrocatalytic coupling has attracted a wide range of research interest achieved considerable developments. Here, is systematically reviewed aiming at reductive cathode oxidative anode. cathodic part, reaction systems, corresponding design principles electrocatalysts for different mechanism studies from experimental theoretical aspects, application‐oriented devices summarized. Anodic offers potential approach replace conventional energy‐demand synthesis protocols, an indispensable part green controllable construction unsaturated C = N C≡N bonds. According principle that electron transfer crucial point in anodic coupling, reactions sorted out based on direct indirect paths, respectively. Finally, challenges outlooks this field proposed. appealing topic electrochemistry possesses infinite possibilities future.

Language: Английский

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Site-specific Umpolung amidation of carboxylic acids via triplet synergistic catalysis

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: July 30, 2021

Abstract Development of catalytic amide bond-forming methods is important because they could potentially address the existing limitations classical using superstoichiometric activating reagents. In this paper, we disclose an Umpolung amidation reaction carboxylic acids with nitroarenes and nitroalkanes enabled by triplet synergistic catalysis FeI 2 , P(V)/P(III) photoredox catalysis, which avoids production byproducts from stoichiometric coupling A wide range acids, including aliphatic, aromatic alkenyl participate smoothly in such reactions, generating structurally diverse amides good yields (86 examples, up to 97% yield). This strategy opens a method challenging regioselectivity issues between nucleophilic functional groups, complements group compatibility protocols. The synthetic robustness demonstrated late-stage modification complex molecules gram-scale applications.

Language: Английский

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Fast Amide Couplings in Water: Extraction, Column Chromatography, and Crystallization Not Required

Organic Letters, Journal Year: 2020, Volume and Issue: 22(15), P. 5737 - 5740

Published: June 23, 2020

In the micelle of PS-750-M, presence 3° amides from surfactant proline linker mimics dimethylformamide, dimethylacetamide, and N-methyl-2-pyrrolidone. The resultant micellar properties enable extremely fast amide couplings mediated by 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide (without hydroxybenzotriazole), rather than expensive specialized coupling agents. Conditions have been developed wherein products precipitate, isolation filtration completely avoids use organic solvent. This methodology is scalable product epimerization.

Language: Английский

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The preparation and applications of amides using electrosynthesis

Green Chemistry, Journal Year: 2020, Volume and Issue: 22(22), P. 7737 - 7759

Published: Jan. 1, 2020

Given the renaissance in organic electrochemistry, a number of novel approaches to synthesis amides have been described that exploit this technique. This tutorial review will explore and critically assess these their associated applications.

Language: Английский

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Visible‐Light‐Mediated Oxidative Amidation of Aldehydes by Using Magnetic CdS Quantum Dots as a Photocatalyst

Chemistry - A European Journal, Journal Year: 2021, Volume and Issue: 27(17), P. 5483 - 5491

Published: Jan. 6, 2021

Abstract A magnetic CdS quantum dot (Fe 3 O 4 /polydopamine (PDA)/CdS) was synthesized through a facile and convenient method from inexpensive starting materials. Characterization of the prepared catalyst performed by means FTIR spectroscopy, XRD, SEM, TEM, energy‐dispersive X‐ray vibrating‐sample magnetometer techniques. Fe /PDA/CdS found to be highly active photocatalyst for amidation aromatic aldehydes using air as clean oxidant under mild conditions. The can recovered separation successfully reused five cycles without considerable loss its catalytic activity.

Language: Английский

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Water: An Underestimated Solvent for Amide Bond-Forming Reactions

ACS Sustainable Chemistry & Engineering, Journal Year: 2022, Volume and Issue: 10(16), P. 5299 - 5306

Published: April 7, 2022

Construction of the amide/peptide bond is one most encountered transformations in pharmaceutical and chemical industries. Traditional protocols rely on use undesirable organic solvents, such as N,N-dimethylformamide (DMF), N-methyl pyrrolidone (NMP), or dichloromethane (CH2Cl2). These solvents adversely impact environment, workers' safety, health. This has led academia industry to search develop greener more sustainable amide forming synthetic increase performance terms yield selectivity avoid reduce dependency these hazardous solvents. The following account discusses recent development formation water.

Language: Английский

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