Organic Process Research & Development最新文献_第8页

Development and Scale-Up of a Regioselective Functionalization of 2-Cyano-3-fluoropyridine in a Flow Reactor 流动反应器中2-氰基-3-氟吡啶区域选择性功能化的开发与规模化

IF 3.3 3区化学

Organic Process Research & Development Pub Date : 2026-08-21 Epub Date: 2026-08-11 DOI: 10.1021/acs.oprd.6c00156

Léna Brassart, Antoine Coeuillas, Maxime Manneveau, Thomas Poisson, Julien Legros, Philippe Huez, Massimiliano Forcato, Philippe Jubault, Laëtitia Chausset-Boissarie

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Ultrasound-Assisted Polymorph Control in Reactive Crystallization of l-Glutamic Acid: Aiming for Consistently Producing Stable Form 超声辅助下l-谷氨酸反应结晶的晶型控制：以稳定晶型为目标

IF 3.3 3区化学

Organic Process Research & Development Pub Date : 2026-08-21 Epub Date: 2026-07-13 DOI: 10.1021/acs.oprd.6c00092

Biyu Zhang, Christos Xiouras, Merve Öner, Georgios D. Stefanidis, Tom Van Gerven

{"title":"Ultrasound-Assisted Polymorph Control in Reactive Crystallization of l-Glutamic Acid: Aiming for Consistently Producing Stable Form","authors":"Biyu Zhang, Christos Xiouras, Merve Öner, Georgios D. Stefanidis, Tom Van Gerven","doi":"10.1021/acs.oprd.6c00092","DOIUrl":"10.1021/acs.oprd.6c00092","url":null,"abstract":"Polymorphic control in reactive crystallization remainsa criticalchallenge due to the stochastic nature of nucleation and the competitionbetween metastable and stable forms. This work aims to investigatethe mechanisms controlling polymorphism in single-feed semibatch reactivecrystallization and to develop strategies for reliably producing thestable form using l-glutamic acid (LGA) as a model compound.Unseeded and seeded experiments were performed under conventionaland ultrasound-assisted conditions at high reactant concentrations.In unseeded systems, the use of ultrasound decreased induction timesbut did not eliminate the stochasticity of polymorphic outcomes. Comparedwith previously studied low-concentration systems yielding nearlypure metastable form, a higher concentration of reactant (sulfuricacid) may promote local supersaturation inhomogeneity, increasingthe stochasticity of polymorphism. Seeded experiments showed thatsufficient seed loading suppressed α-form nucleation and favoredgrowth and secondary nucleation of β-form, though seeding athigher supersaturation required more seeds. Combining ultrasound withseeds significantly reduced the seed loading required and reproduciblyproduced, within the investigated repetitions, stable β-LGAcrystals by enhancing secondary nucleation and overcoming the kineticadvantage of the metastable form. These findings provide deeper insightinto the stochastic nucleation of the polymorphs and demonstrate ultrasoundas a promising process-intensification tool for robustly producingthe stable form during reactive crystallization.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"30 8","pages":"2212–2227"},"PeriodicalIF":3.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148476545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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An Aryl Alcohol Oxidase-Peroxygenase Catalyst System Enables Efficient Alcohol to Aldehyde Transformation 芳醇氧化酶-过氧酶催化体系实现醇醛高效转化

IF 3.3 3区化学

Organic Process Research & Development Pub Date : 2026-08-21 Epub Date: 2026-07-22 DOI: 10.1021/acs.oprd.6c00056

Yutong Wang, Nure Celebi, Paul Kerstholt, Sebastian Govaerts, Vlada B. Urlacher, Miguel Alcalde, Frank Hollmann

{"title":"An Aryl Alcohol Oxidase-Peroxygenase Catalyst System Enables Efficient Alcohol to Aldehyde Transformation","authors":"Yutong Wang, Nure Celebi, Paul Kerstholt, Sebastian Govaerts, Vlada B. Urlacher, Miguel Alcalde, Frank Hollmann","doi":"10.1021/acs.oprd.6c00056","DOIUrl":"10.1021/acs.oprd.6c00056","url":null,"abstract":"We describe a scalable aryl alcohol oxidase-based alcoholoxidationplatform using multiphase and microaqueous reaction formats. Using trans-2-hexen-1-ol as a model substrate, a 9:1 n-dodecane/buffer two-liquid-phase system (100 mL, 0.55 M substrate)delivered up to ∼0.42 M trans-2-hexen-1-alwith initial space-time yields up to 33 mM h–1 andexceptionally high TTN (up to 3.6 × 106). Unexpectedly,catalase did not improve productivity, whereas replacing catalasewith a peroxygenase enabled direct utilization of H2O2 and increased the initial rate by >67% without compromisingselectivity. Celite immobilization afforded a highly productive microaqueoussystem and enabled semipreparative operation in a rotating-bed reactor(120 mL, ∼1.5 M substrate), reaching 1.2 M aldehyde (≈120g L–1) with near-linear accumulation for ∼48h. Overall, the titers, space-time yields, and TTN achieved here clearlyrival chemical oxidation processes, highlighting strong potentialfor preparative-scale aldehyde manufacture.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"30 8","pages":"2159–2166"},"PeriodicalIF":3.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148564926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Process-Intensified Continuous Flow Synthesis of Propofol 工艺强化连续流合成异丙酚

IF 3.3 3区化学

Organic Process Research & Development Pub Date : 2026-08-21 Epub Date: 2026-07-11 DOI: 10.1021/acs.oprd.6c00151

Antoine Coeuillas, Aurore Ceuninck, Laetitia Chausset-Boissarie, Julien Legros, Philippe Jubault, Thomas Poisson

{"title":"Process-Intensified Continuous Flow Synthesis of Propofol","authors":"Antoine Coeuillas, Aurore Ceuninck, Laetitia Chausset-Boissarie, Julien Legros, Philippe Jubault, Thomas Poisson","doi":"10.1021/acs.oprd.6c00151","DOIUrl":"https://doi.org/10.1021/acs.oprd.6c00151","url":null,"abstract":"This work presents a significantly improved and scaledcontinuousflow process for the synthesis of propofol (2,6-diisopropylphenol),a WHO-essential anesthetic agent. Building upon previous research,the two-step synthesis featuring a Friedel–Crafts bisalkylationof 4-hydroxybenzoic acid followed by base-mediated decarboxylationwas reoptimized, taking into consideration critical industrial constraintssuch as solvent toxicity, reagent cost, productivity, and processrobustness, leading to substantially reduced residence time and enhancedproductivity through strategic modifications including neat isopropanolinjection, adoption of a greener glycerol-based solvent system withpotassium hydroxide, and implementation of kilolab-/pilot-scale equipment.The scaled-up process demonstrates remarkable space-time yield exceeding2 kg·h–1·L–1 for thebisalkylation step and overall productivities surpassing previouslyreported methods. This advancement makes a step forward to a realisticpathway for more sustainable and decentralized manufacturing of thiscritical pharmaceutical compound.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"30 8","pages":"2296–2307"},"PeriodicalIF":3.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148810337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Discovery Process Chemistry (DPC) Model: A Cross-Pharma Perspective 发现过程化学（DPC）模型：一个跨制药的视角

IF 3.3 3区化学

Organic Process Research & Development Pub Date : 2026-08-21 Epub Date: 2026-07-17 DOI: 10.1021/acs.oprd.6c00218

Joseph M. Bateman, Jonathan M. E. Hughes, Matthieu Jouffroy, Peter J. Lindsay-Scott, Thomas M. McGuire, Damien Valette, Hilmar Weinmann

引用次数: 0

Modular and Scalable Alluvial Cells for the Electroconversion of Poorly Soluble l-Cystine 用于电转化难溶l-胱氨酸的模块化和可扩展冲积电池

IF 3.3 3区化学

Organic Process Research & Development Pub Date : 2026-08-21 Epub Date: 2026-07-17 DOI: 10.1021/acs.oprd.6c00197

Marola S. Lenhard, Ragnar Bogner, Ricarda Kollmuß, Stefan Haufe, Siegfried R. Waldvogel

引用次数: 0

Dehydrative Coupling of Carboxylic Acids with Amines in the Presence of Sodium Azepane-1-carbodithioate 氮杂烷-1-碳二硫酸钠存在下羧酸与胺的脱水偶联

IF 3.3 3区化学

Organic Process Research & Development Pub Date : 2026-08-21 Epub Date: 2026-07-17 DOI: 10.1021/acs.oprd.6c00193

Ayhan Yıldırım

引用次数: 0

Embracing PMI: Advancing Sustainability in Peptide Synthesis 拥抱PMI：推进肽合成的可持续性

IF 3.3 3区化学

Organic Process Research & Development Pub Date : 2026-08-21 Epub Date: 2026-07-20 DOI: 10.1021/acs.oprd.6c00206

Anamika Sharma, Ashish Kumar, L. Ravithej Singh, Priyanka Kushwaha, Beatriz G. de la Torre, Fernando Albericio

{"title":"Embracing PMI: Advancing Sustainability in Peptide Synthesis","authors":"Anamika Sharma, Ashish Kumar, L. Ravithej Singh, Priyanka Kushwaha, Beatriz G. de la Torre, Fernando Albericio","doi":"10.1021/acs.oprd.6c00206","DOIUrl":"10.1021/acs.oprd.6c00206","url":null,"abstract":"Process mass intensity (PMI) and complete E-factor (cEF)are widelyaccepted metrics for evaluating the sustainability of chemical processes,yet their routine application in peptide synthesis remains limited.This is primarily due to the perceived complexity and time requiredfor mass accounting across repetitive coupling/deprotection cyclesand solvent-intensive operations characteristic of both SPPS and LPPS.In this work, we present a simplified and practical approach for therapid calculation of PMI and cEF specifically tailored to peptidesynthesis workflows. The method is implemented through a user-friendlyExcel-based tool that converts routinely recorded experimental parameterssuch as reaction scale, resin loading/tag, reagent, and solvent consumptioninto quantitative sustainability metrics using built-in formulas.The streamlined workflow allows PMI and cEF to be calculated withinminutes without the need for specialized software or extensive additionaldata collection. By lowering the barrier to quantitative sustainabilityassessment, this method facilitates the routine inclusion of greenmetrics in method development, process optimization, and reporting.Importantly, the approach is equally relevant to academic and industriallaboratories, supporting informed decision-making and fostering thebroader adoption of sustainability principles in peptide synthesis.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"30 8","pages":"2346–2359"},"PeriodicalIF":3.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148564928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Synthetic Role of PFAS in Drug Substance Manufacturing: An IQ Consortium Working Group Review on the Potential Impact of PFAS Restrictions on Patient Access to Medicines PFAS在原料药生产中的合成作用：一个IQ联盟工作组审查PFAS限制对患者获得药物的潜在影响

IF 3.3 3区化学

Organic Process Research & Development Pub Date : 2026-08-21 Epub Date: 2026-07-29 DOI: 10.1021/acs.oprd.6c00114

Gemma Scotney, Kenneth J. Fraunhoffer, Ankur Jalan, Dazhan Liu, Andreas R. Rötheli, Robert Toner, Jonathan C. Tripp, Xin Yao

{"title":"The Synthetic Role of PFAS in Drug Substance Manufacturing: An IQ Consortium Working Group Review on the Potential Impact of PFAS Restrictions on Patient Access to Medicines","authors":"Gemma Scotney, Kenneth J. Fraunhoffer, Ankur Jalan, Dazhan Liu, Andreas R. Rötheli, Robert Toner, Jonathan C. Tripp, Xin Yao","doi":"10.1021/acs.oprd.6c00114","DOIUrl":"10.1021/acs.oprd.6c00114","url":null,"abstract":"Per- and polyfluoroalkylsubstances (PFAS) have beenwidely usedin consumer and industrial applications including the pharmaceuticalindustry. This widespread adoption throughout society has recentlycome under scrutiny due to human health and environmental concernsassociated with the toxicity and environmental persistence of certainPFAS. Within the IQ Consortium, a Working Group (WG) focusing on drugsubstance manufacturing has been established to assess the prevalenceof PFAS in commercial drug substance manufacturing and the potentialimpact of PFAS regulations on patient access to medicines. To addressgaps in current definitions, we introduce a functional classification─visible,contributing, and invisible PFAS─to distinguish PFAS presentin marketed active pharmaceutical ingredients (APIs), those essentialfor installing PFAS moieties into APIs, and reagents or solvents enablingsynthesis without remaining in the final product. Survey data fromIQ Consortium member companies and literature analysis confirm extensivePFAS use and presence across the drug substance supply chain. Thesefindings highlight that broad PFAS restrictions could disrupt manufacturing,necessitate significant process redevelopment and regulatory revalidation,and jeopardize continuity of supply. Proactive engagement and riskmitigation strategies are critical to balance environmental objectiveswith uninterrupted patient access to essential medicines.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"30 8","pages":"2233–2244"},"PeriodicalIF":3.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148665872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lipophilic Salts of High Melting Point Drugs Modulate Solid-State Properties and Organic Solubility to Enable Manufacturability of Amorphous Solid Dispersions 高熔点药物的亲脂盐调节固态性质和有机溶解度，使无定形固体分散体的可制造性

IF 3.3 3区化学

Organic Process Research & Development Pub Date : 2026-08-21 Epub Date: 2026-08-06 DOI: 10.1021/acs.oprd.6c00079

Stella P. Petrova, Matthew M. Behymer, Naga K. Duggirala, Aaron Goodwin, Dana E. Moseson-Tarrh, Lynne S. Taylor

{"title":"Lipophilic Salts of High Melting Point Drugs Modulate Solid-State Properties and Organic Solubility to Enable Manufacturability of Amorphous Solid Dispersions","authors":"Stella P. Petrova, Matthew M. Behymer, Naga K. Duggirala, Aaron Goodwin, Dana E. Moseson-Tarrh, Lynne S. Taylor","doi":"10.1021/acs.oprd.6c00079","DOIUrl":"10.1021/acs.oprd.6c00079","url":null,"abstract":"Amorphous solid dispersion(ASD) manufacturability isconstrainedby active pharmaceutical ingredient physicochemical properties; highmelting point (Tm) and high glass transitiontemperature (Tg) limit hot-melt extrusion(HME), and low organic solubility limits spray-drying (SD) throughput.We evaluated lipophilic counterion choice as a solid-state designlever to enable ASD manufacturability by SD or HME. Nine lipophilicsalts of atazanavir (ATZ) and mebendazole (MBZ) were prepared withsulfate and sulfonate counterions spanning a range of chain lengthsand steric bulk, and characterized by 1H nuclear magneticresonance spectroscopy, powder X-ray diffraction, differential scanningcalorimetry, and polarized light microscopy. Lipophilic salts showed Tm and Tg reductionsrelative to their free base, with Tg reductionsof up to approximately 30 °C. Organic solubility in ethanol,acetone, and tetrahydrofuran improved 2–15× or greateracross most salt-solvent combinations. Vacuum compression moldingconfirmed that a representative lipophilic salt (ATZ-pTSA) enablesthermal amorphization at HME-relevant processing temperatures, wherethe ATZ free base does not fully melt or dissolve into the model polymer.Counterion choice functions as a solid-state design lever for ASDmanufacturability through a proposed lattice-packing disruption mechanismthat simultaneously reduces Tm and Tg and improves organic solubility.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"30 8","pages":"2179–2193"},"PeriodicalIF":3.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148692512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0