Low-Temperature Continuous Mechanochemical Synthesis of Hydantoin-Based Active Pharmaceutical Ingredients by Spiral Gas–Solid Two-Phase Flow DOI

Yong Song,

Zhiyuan Jin, Jinsong Li

и другие.

ACS Sustainable Chemistry & Engineering, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 21, 2024

Although the mechanochemical synthesis of many active pharmaceutical ingredients (APIs) has been demonstrated, a technology that enables large-scale continuous thermosensitive APIs is lacking. In this work, we investigated low-temperature series hydantoin-based derivatives, including nitrofurantoin and dantrolene, by using previously proposed spiral gas–solid two-phase flow (S-GSF) technique. The structures prepared products were determined Fourier transform infrared spectroscopy, nuclear magnetic resonance, powder X-ray diffractometry. Results showed not drop organic solvent was used for entire process, high yields (not less than 94%) E-isomer pure compounds obtained without complex purification step. Even with low melting point raw material 5-nitrofurfural, could be synthesized continuously remarkable amorphization. This situation distinguishes S-GSF from existing methods. addition, improving system reactivity through cocrystallization highly efficient technology, complete conversion dantrolene achieved first time, corresponding space-time yield up to 7.5 × 104 kg m–3 day–1. particular, crystalline form in way substable dantr-V.

Язык: Английский

Salient Achievements in Synthetic Organic Chemistry Enabled by Mechanochemical Activation DOI
Eusebio Juaristi, C.G. Ávila-Ortíz

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

Процитировано

52
Accelerated enzyme engineering by machine-learning guided cell-free expression DOI Creative Commons
Grant M. Landwehr, Jonathan W. Bogart,

Carol Magalhaes

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 20, 2025

Язык: Английский

Процитировано

11
Sustainable Beckmann Rearrangement using Bead‐Milling Technology: The Route to Paracetamol DOI Creative Commons

Romain Geib,

Evelina Colacino, Ludovic Gremaud

и другие.

ChemSusChem, Год журнала: 2024, Номер 17(12)

Опубликована: Фев. 14, 2024

To address the growing demand for more sustainable and greener chemistry, mechanochemical methodologies are emerging as key players. However, to date there has been little data highlighting benefits of these rising technologies with regard process scale-up activities or implementation in commercial production scale. Herein, we report first application bead-mill technology (Dyno®-mill) synthesis Acetaminophen, known under brand name Paracetamol. Using Beckmann rearrangement, optimized solvent-free methodology delivered a final product on scale several tens grams. In comparison current solvent-based process, proposed achieves higher yield while also allowing removal solvents chemical reaction, hereby reducing one extensive drivers waste generation. The approach was compared using combination green metrics EcoScale score. paracetamol scores highest all over currently used solution-based processes.

Язык: Английский

Процитировано

7
Batch and continuous flow mechanochemical synthesis of organic compounds including APIs DOI

Ranjit S. Atapalkar,

Amol A. Kulkarni

Reaction Chemistry & Engineering, Год журнала: 2023, Номер 9(1), С. 10 - 25

Опубликована: Сен. 5, 2023

Mechanochemistry is becoming an enabling technology for the synthesis of organic and inorganic compounds as well polymers it underlines sustainability in a significant manner.

Язык: Английский

Процитировано

10
Solvent Replacement Strategies for Processing Pharmaceuticals and Bio-Related Compounds—A Review DOI Creative Commons
Jia Lin Lee, Gun Hean Chong, Masaki Ota

и другие.

Liquids, Год журнала: 2024, Номер 4(2), С. 352 - 381

Опубликована: Апрель 9, 2024

An overview of solvent replacement strategies shows that there is great progress in green chemistry for replacing hazardous di-polar aprotic solvents, such as N,N-dimethylformamide (DMF), 1-methyl-2-pyrrolidinone (NMP), and 1,4-dioxane (DI), used processing active industrial ingredients (APIs). In synthetic chemistry, alcohols, carbonates, ethers, eucalyptol, glycols, furans, ketones, cycloalkanones, lactones, pyrrolidinone or mixtures, 2-methyl tetrahydrofuran methanol, HCl cyclopentyl methyl ether, trifluoroacetic acid propylene carbonate surfactant water (no organic solvents) are suggested solvents. For the dichloromethane (DCM) chromatography, ethyl acetate ethanol 2-propanol heptanes, with without acetic ammonium hydroxide additives, suggested, along methanol tert-butyl cyclohexane, CO2-ethyl acetate, CO2-methanol, CO2-acetone, CO2-isopropanol. Supercritical CO2 (scCO2) can be to replace many solvents materials from natural sources. Vegetable, drupe, legume, seed oils co-extractants (mixed substrate before extraction) typical co-solvents (ethanol, acetone) scCO2 extraction. Mixed consisting a hydrogen bond donor (HBD) acceptor (HBA) not addressed GSK CHEM21 guides. Published data 100 water-soluble water-insoluble APIs mono-solvents show polarity ranges appropriate mixed When used, possible HBA candidate acetone, acid, acetonitrile, ethanol, tetrahydrofuran, 2,2,5,5-tetramethyloxolane, dimethylisosorbide, Cyrene, Cygnet 0.0, diformylxylose. alcohol candidates cyclopentanone, esters, lactone, eucalytol, MeSesamol, HBA—HBA Cyrene—Cygnet could provide interesting new combinations. Solubility parameters, Reichardt polarity, Kamlet—Taft linear solvation energy relationships practical ways identifying applicable API systems.

Язык: Английский

Процитировано

4
Accelerated enzyme engineering by machine-learning guided cell-free expression DOI Creative Commons
Grant M. Landwehr, Jonathan W. Bogart,

Carol Magalhaes

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 2, 2024

Enzyme engineering is limited by the challenge of rapidly generating and using large datasets sequence-function relationships for predictive design. To address this challenge, we developed a machine learning (ML)-guided platform that integrates cell-free DNA assembly, gene expression, functional assays to map fitness landscapes across protein sequence space optimize enzymes multiple, distinct chemical reactions. We applied engineer amide synthetases evaluating substrate preference 1,217 enzyme variants in 10,953 unique used these data build augmented ridge regression ML models predicting synthetase capable making 9 small molecule pharmaceuticals. Our ML-guided, framework promises accelerate enabling iterative exploration specialized biocatalysts parallel.

Язык: Английский

Процитировано

4
Direct amidation of acids in a screw reactor for the continuous flow synthesis of amides DOI

Ranjit S. Atapalkar,

Amol A. Kulkarni

Chemical Communications, Год журнала: 2023, Номер 59(60), С. 9231 - 9234

Опубликована: Янв. 1, 2023

A simple and efficient solvent-free protocol for continuous flow synthesis of amides at room temperature is developed using easily available starting materials.

Язык: Английский

Процитировано

9
Synthesis of Peptides by Reactive Extrusion. Application to the Continuous and Solventless Preparation of Aspartame. DOI Creative Commons

Tharwat Mohy El‐Dine,

Matthieu Lavayssiere, Hélène Adihou

и другие.

ChemistryEurope, Год журнала: 2024, Номер 2(3-4)

Опубликована: Март 25, 2024

Abstract The solventless synthesis of peptides from unactivated amino acids was optimized in a twin‐screw extruder (TSE). general method enabled the preparation dipeptides and tripeptides with no epimerization. This flow mechanochemistry approach applied to aspartame, synthetic dipeptide, prepared continuous mode on large scale high productivity.

Язык: Английский

Процитировано

3
Ultrafast Synthesis of Moclobemide via Free Radicals: An Integral Activity in the Heterocyclic Chemistry Lab DOI

Elizabeth Carmona-Quintana,

Josué Rodríguez-Lozada,

Angel Zamudio‐Medina

и другие.

Journal of Chemical Education, Год журнала: 2025, Номер unknown

Опубликована: Апрель 2, 2025

Язык: Английский

Процитировано

0
Supramolecular intermediates in thermo-mechanochemical direct amidations DOI Creative Commons
Tomislav Stolar, Jasna Alić, Gregor Talajić

и другие.

Chemical Communications, Год журнала: 2023, Номер 59(90), С. 13490 - 13493

Опубликована: Янв. 1, 2023

We present a solvent-free thermo-mechanochemical approach for the direct coupling of carboxylic acids and amines, which avoids activators additives. Non-covalent interactions between reagents guide formation amide bond.

Язык: Английский

Процитировано

8