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超越简单研磨:氯化铵促进去铁酮的可持续、无柱机械化学合成。

Beyond Simple Grinding: Methylammonium Chloride Promotes Sustainable, Cylinder-Free Mechanochemical Synthesis of Deferiprone.

作者信息

Basoccu Francesco, Piermarini Sara, Angelini Tommaso, Mari Massimiliano, Mariani Edoardo, Falchi Alessandro, Porcheddu Andrea

机构信息

Dipartimento di Scienze Chimiche e Geologiche, Università degli Studi di Cagliari, Cittadella Universitaria Monserrato, S.P. Monserrato-Sestu Km 0,700, 09042, Monserrato, CA, Italy.

Centro Ricerche-Chiesi Farmaceutici S.p.A, Largo Belolli 11/a, 43126, Parma, PR, Italy.

出版信息

ChemSusChem. 2025 Aug 6;18(16):e202500457. doi: 10.1002/cssc.202500457. Epub 2025 Jul 14.

DOI:10.1002/cssc.202500457
PMID:40569205
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12330328/
Abstract

Thalassemias are a group of inherited hemoglobinopathies that disrupt normal hemoglobin synthesis. Managing these conditions often involves regular blood transfusions and iron chelation therapy to mitigate iron overload. Among the available chelators, deferoxamine, deferasirox, and deferiprone, the latter stands out notably for its use when other drugs are ineffective or intolerable for patients. Although the synthesis of deferiprone is well-documented, traditional methods typically involve lengthy reaction times and environmentally harmful conditions. This study investigates mechanochemistry as a more sustainable, efficient, and eco-friendly alternative. Deferiprone is successfully synthesized and the production process is optimized by employing solid-state techniques, thereby reducing reaction time, energy consumption, and environmental impact. These findings pave the way for cleaner and more sustainable manufacturing pathways for this critical agent in thalassemia management.

摘要

地中海贫血是一组遗传性血红蛋白病,会干扰正常的血红蛋白合成。治疗这些病症通常需要定期输血和铁螯合疗法,以减轻铁过载。在现有的螯合剂中,去铁胺、地拉罗司和去铁酮,后者因其在其他药物对患者无效或无法耐受时的使用而格外突出。尽管去铁酮的合成已有充分记录,但传统方法通常反应时间长且环境危害大。本研究探索机械化学作为一种更具可持续性、高效且环保的替代方法。通过采用固态技术成功合成了去铁酮并优化了生产过程,从而减少了反应时间、能源消耗和环境影响。这些发现为这种地中海贫血治疗关键药物开辟了更清洁、更可持续的制造途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6081/12330328/c1a319ecfbf7/CSSC-18-e202500457-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6081/12330328/434a22d7d375/CSSC-18-e202500457-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6081/12330328/93092735610f/CSSC-18-e202500457-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6081/12330328/7318425e1064/CSSC-18-e202500457-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6081/12330328/eebfc1bf6c23/CSSC-18-e202500457-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6081/12330328/ba5ea4732527/CSSC-18-e202500457-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6081/12330328/aaaaf0e759cb/CSSC-18-e202500457-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6081/12330328/c1a319ecfbf7/CSSC-18-e202500457-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6081/12330328/434a22d7d375/CSSC-18-e202500457-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6081/12330328/93092735610f/CSSC-18-e202500457-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6081/12330328/7318425e1064/CSSC-18-e202500457-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6081/12330328/eebfc1bf6c23/CSSC-18-e202500457-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6081/12330328/ba5ea4732527/CSSC-18-e202500457-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6081/12330328/aaaaf0e759cb/CSSC-18-e202500457-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6081/12330328/c1a319ecfbf7/CSSC-18-e202500457-g003.jpg

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本文引用的文献

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Mechanochemistry: Unravelling the Impact of Metal Leaching in Organic Synthesis.机械化学:揭示金属浸出在有机合成中的影响
ChemSusChem. 2025 May 19;18(10):e202402547. doi: 10.1002/cssc.202402547. Epub 2025 Jan 30.
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Synthesis without solvent: consequences for mechanochemical reactivity.无溶剂合成:对机械化学反应性的影响
Chem Commun (Camb). 2023 Nov 30;59(96):14210-14222. doi: 10.1039/d3cc04929a.
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Mechanochemistry for Healthcare: Revealing the Nitroso Derivatives Genesis in the Solid State.用于医疗保健的机械化学:揭示固态亚硝基衍生物的起源
ChemSusChem. 2024 Feb 8;17(3):e202301034. doi: 10.1002/cssc.202301034. Epub 2023 Nov 20.
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Green metrics in mechanochemistry.机械化学中的绿色指标
Chem Soc Rev. 2023 Oct 2;52(19):6680-6714. doi: 10.1039/d2cs00997h.
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Thalassemia Major and Associated Psychosocial Problems: A Narrative Review.重型地中海贫血及相关心理社会问题:叙述性综述
Iran J Public Health. 2022 Jan;51(1):12-18. doi: 10.18502/ijph.v51i1.8287.
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Boronic-Acid-Accelerated Electrophilic Activation of Unprotected Maltols to N-Substituted Hydroxypyridinones in Water.硼酸加速未保护麦芽醇在水中与N-取代羟基吡啶酮的亲电活化反应。
Org Lett. 2022 Feb 18;24(6):1263-1267. doi: 10.1021/acs.orglett.1c03833. Epub 2022 Feb 5.
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Current status of beta-thalassemia and its treatment strategies.β-地中海贫血的现状及其治疗策略。
Mol Genet Genomic Med. 2021 Dec;9(12):e1788. doi: 10.1002/mgg3.1788. Epub 2021 Nov 5.
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Sustainability Assessment of Mechanochemistry by Using the Twelve Principles of Green Chemistry.采用绿色化学十二原则对机械化学进行可持续性评估。
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Discovery of -Aryl-pyridine-4-ones as Novel Potential Agrochemical Fungicides and Bactericides.发现 -芳基-吡啶-4-酮类新型农用杀菌剂和杀细菌剂。
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