Salient Achievements in Synthetic Organic Chemistry Enabled by Mechanochemical Activation

Synthesis, Год журнала: 2023, Номер 55(16), С. 2439 - 2459

Опубликована: Май 3, 2023

Abstract Although known for millennia, it is only recently that mechanochemistry has received serious attention by chemists. Indeed, during the past 15 years an extraordinary number of reports concerning solid-state chemical transformations through grinding and milling techniques have been recorded. This short review discusses circumstances led this renaissance, highlighting present intense interest in so-called green chemistry, enabling capacity to handle insoluble substrates, identification profound influence additives can on mechanochemically activated reactions. The core account focuses salient developments synthetic organic especially amino acid peptide­ mechanosynthesis, successful employment mechanochemical activation combination with asymmetric organocatalysis, promising enzymatic whole cell biocatalysis, remarkable achievement multicomponent selective reactions via complex, multistep reaction pathways, mechanosynthesis representative heterocycles. final section comments some pending tasks area, such as scaling-up processes be practical use industry, requirement easier more efficient control parameters monitoring devices, consequently careful analysis additional procedures a proper understanding phenomena. 1 Introduction 2 Brief History Mechanochemistry 3 Milling Equipment Reaction Parameters 4 Attributes That Propelled Its Present Renaissance 4.1 Enormous Attention Being Presently Paid Sustainable Chemistry 4.2 Reduced Energy Consumption 4.3 Additive-Based 4.4 Handling Insoluble Reactants 4.5 ‘Impossible’ Reactions Are Successful 4.6 Air- Water-Sensitive Reagents Ball 5 Salient Developments Mechanochemical Activation Synthetic Organic 5.1 Amino Acid Peptide Mechanosynthesis 5.2 Asymmetric Synthesis Organocatalysis under Ball-Milling Conditions 5.3 Mechanoenzymology 5.4 Multicomponent Activated 5.5 Heterocycles Modification 6 Future Directions 6.1 Scaling-Up Protocols 6.2 Temperature-Controlled 6.3 Understanding Transformations 6.4 Emerging Techniques 7 Conclusions

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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Biomass-Derived Solvents for Sustainable Transition Metal-Catalyzed C–H Activation

ACS Sustainable Chemistry & Engineering, Год журнала: 2019, Номер 7(9), С. 8023 - 8040

Опубликована: Март 29, 2019

Transition metal-catalyzed C–H activation has emerged as an increasingly powerful strategy in molecular syntheses and a particularly attractive alternative to classical methods of cross-couplings. During the recent years, significant focus been dedicated further improve sustainable nature approach. As solvents represent major portion organic pollution caused by chemical syntheses, range nontoxic, biobased, have developed substitute for common reaction media. In this review, we present general perspective biomass-derived transition reactions their unique potential up January 2019.

Язык: Английский

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Solvent-Free, Continuous Synthesis of Hydrazone-Based Active Pharmaceutical Ingredients by Twin-Screw Extrusion

ACS Sustainable Chemistry & Engineering, Год журнала: 2020, Номер 8(32), С. 12230 - 12238

Опубликована: Авг. 5, 2020

Twin-screw extrusion (TSE) was used to synthesize hydantoin-based active pharmaceutical ingredients (APIs) such as nitrofurantoin and dantrolene, employing minimal or no solvent. Postsynthetic workup not required. This work demonstrates that solvent-free synthesis can be conducted in a continuous manner for products.

Язык: Английский

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Greening the synthesis of peptide therapeutics: an industrial perspective

RSC Advances, Год журнала: 2020, Номер 10(69), С. 42457 - 42492

Опубликована: Янв. 1, 2020

This review highlights the efforts made to date promote greener peptide synthesis, from an industrial perspective.

Язык: Английский

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Green strategies for transition metal-catalyzed C–H activation in molecular syntheses

Organic Chemistry Frontiers, Год журнала: 2021, Номер 8(17), С. 4886 - 4913

Опубликована: Янв. 1, 2021

Sustainable strategies for the activation of inert C–H bonds towards improved resource-economy.

Язык: Английский

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Mechanochemical Grignard Reactions with Gaseous CO₂ and Sodium Methyl Carbonate**

Angewandte Chemie International Edition, Год журнала: 2021, Номер 61(9)

Опубликована: Дек. 23, 2021

Abstract A one‐pot, three‐step protocol for the preparation of Grignard reagents from organobromides in a ball mill and their subsequent reactions with gaseous carbon dioxide (CO 2 ) or sodium methyl carbonate providing aryl alkyl carboxylic acids up to 82 % yield is reported. Noteworthy are short reaction times significantly reduced solvent amounts [2.0 equiv. liquid assisted grinding (LAG) conditions]. Unexpectedly, bromides methoxy substituents lead symmetric ketones as major products.

Язык: Английский

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Mechanochemical C−X/C−H Functionalization: An Alternative Strategic Access to Pharmaceuticals

European Journal of Organic Chemistry, Год журнала: 2022, Номер 2022(8)

Опубликована: Янв. 11, 2022

Abstract In the pursuit of clean pharmaceutical production, chemists in medicinal industry require access to new sustainable methodologies reduce and even eliminate pollution, which is mainly produced by overuse organic solvents during chemical synthesis active ingredients (APIs). this context, solvent‐free/less mechanochemical functionalization small molecules has gradually emerged as a powerful strategy for green modification APIs, bioactive compounds, functional materials. review, we present an overview C−X/C−H applications chemistry, involving cross‐coupling, cross‐dehydrogenative coupling, oxidative coupling (via C−H activation pathway), direct radical pathway) key steps preparation APIs compounds.

Язык: Английский

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Solid‐State Enzymatic Hydrolysis of Mixed PET/Cotton Textiles**

ChemSusChem, Год журнала: 2022, Номер 16(1)

Опубликована: Сен. 27, 2022

Waste polyester textiles are not recycled due to separation challenges and partial structural degradation during use recycling. Chemical recycling of polyethylene terephthalate (PET) through depolymerization can provide a feedstock monomers make "as-new" polymers. While enzymatic PET is more selective sustainable approach, methods in development, however, have thus far been limited clean, high-quality feedstocks, require an energy-intensive melt-amorphization step ahead treatment. Here, high-crystallinity mixed PET/cotton could be directly selectively depolymerized terephthalic acid (TPA) by using commercial cutinase from Humicola insolens under moist-solid reaction conditions, affording up 30±2 % yield TPA. The process was readily combined with cotton simultaneous or sequential application the cellulase enzymes CTec2®, providing 83±4 glucose without any negative influence on TPA yield.

Язык: Английский

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Mechanochemical Synthesis of Aryl Fluorides by Using Ball Milling and a Piezoelectric Material as the Redox Catalyst

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(39)

Опубликована: Июль 31, 2023

Abstract Aryl fluorides are important structural motifs in many pharmaceuticals. Although the Balz–Schiemann reaction provides an entry to aryl from aryldiazonium tetrafluoroborates, it suffers drawbacks such as long time, high temperature, toxic solvent, gas release, and low functional group tolerance. Here, we describe a general method for synthesis of tetrafluoroborates using piezoelectric material redox catalyst under ball milling conditions presence Selectfluor. This approach effectively addresses aforementioned limitations. Furthermore, can be recycled multiple times. Mechanistic investigations indicate that this fluorination may proceed via radical pathway, Selectfluor plays dual role both source fluorine terminal reductant.

Язык: Английский

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