Replacement of Less-Preferred Dipolar Aprotic and Ethereal Solvents in Synthetic Organic Chemistry with More Sustainable Alternatives

Chemical Reviews, Год журнала: 2022, Номер 122(6), С. 6749 - 6794

Опубликована: Фев. 24, 2022

Dipolar aprotic and ethereal solvents comprise just over 40% of all organic utilized in synthetic organic, medicinal, process chemistry. Unfortunately, many the common "go-to" are considered to be "less-preferable" for a number environmental, health, safety (EHS) reasons such as toxicity, mutagenicity, carcinogenicity, or practical handling flammability volatility. Recent legislative changes have initiated implementation restrictions on use commonly employed dipolar dimethylformamide (DMF) N-methyl-2-pyrrolidinone (NMP), ethers 1,4-dioxane. Thus, with growing legislative, EHS, societal pressures, need identify implement alternative that greener, safer, more sustainable has never been greater. Within this review, ubiquitous nature is discussed respect physicochemical properties made them so appealing chemists. An overview current being imposed discussed. A variety alternative, garnered attention past decade then examined, case studies examples where less-preferable successfully replaced safer highlighted. Finally, general guidance solvent selection replacement included Supporting Information review.

Язык: Английский

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Emerging Trends in Cross-Coupling: Twelve-Electron-Based L₁Pd(0) Catalysts, Their Mechanism of Action, and Selected Applications

Chemical Reviews, Год журнала: 2022, Номер 122(23), С. 16983 - 17027

Опубликована: Окт. 3, 2022

Monoligated palladium(0) species, L

Язык: Английский

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Peptides as Therapeutic Agents: Challenges and Opportunities in the Green Transition Era

Molecules, Год журнала: 2023, Номер 28(20), С. 7165 - 7165

Опубликована: Окт. 19, 2023

Peptides are at the cutting edge of contemporary research for new potent, selective, and safe therapeutical agents. Their rise has reshaped pharmaceutical landscape, providing solutions to challenges that traditional small molecules often cannot address. A wide variety natural modified peptides have been obtained studied, many others advancing in clinical trials, covering multiple therapeutic areas. As demand peptide-based therapies grows, so does need sustainable environmentally friendly synthesis methods. Traditional peptide synthesis, while effective, involves draining processes, generating significant waste consuming vast resources. The integration green chemistry offers alternatives, prioritizing eco-friendly reduction, energy conservation. This review delves into transformative potential applying principles by discussing relevant examples application such approaches production active ingredients (APIs) with a structure how these efforts critical an effective transition era field.

Язык: Английский

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

Organic Process Research & Development, Год журнала: 2022, Номер 26(6), С. 1562 - 1689

Опубликована: Июнь 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.

Язык: Английский

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Introducing Savie: A Biodegradable Surfactant Enabling Chemo- and Biocatalysis and Related Reactions in Recyclable Water

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(7), С. 4266 - 4278

Опубликована: Фев. 8, 2023

Savie is a biodegradable surfactant derived from vitamin E and polysarcosine (PSar) developed for use in organic synthesis recyclable water. This includes homogeneous catalysis (including examples employing only ppm levels of catalyst), heterogeneous catalysis, biocatalytic transformations, including multistep chemoenzymatic sequence. Use frequently leads to significantly higher yields than do conventional surfactants, while obviating the need waste-generating solvents.

Язык: Английский

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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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Aqueous Micelles as Solvent, Ligand, and Reaction Promoter in Catalysis

JACS Au, Год журнала: 2024, Номер 4(2), С. 301 - 317

Опубликована: Янв. 16, 2024

Water is considered to be the most sustainable and safest solvent. Micellar catalysis a significant contributor chemistry in water. It promotes pathways involving water-sensitive intermediates transient catalytic species under micelles' shielding effect while also replacing costly ligands dipolar-aprotic solvents. However, there lack of critical information about micellar catalysis. This includes why it works better than traditional organic solvents, specific rules differ from those conventional catalysis, how limitations can addressed future. Perspective aims highlight current gaps our understanding provide an analysis designer surfactants' origin essential components. will fundamental including aqueous micelles simultaneously perform multiple functions such as solvent, ligand, reaction promoter.

Язык: Английский

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Recent advances on micellar catalysis in water

Advances in Colloid and Interface Science, Год журнала: 2020, Номер 287, С. 102299 - 102299

Опубликована: Окт. 26, 2020

Язык: Английский

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Water: An Underestimated Solvent for Amide Bond-Forming Reactions

ACS Sustainable Chemistry & Engineering, Год журнала: 2022, Номер 10(16), С. 5299 - 5306

Опубликована: Апрель 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.

Язык: Английский

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