An Optimized Scalable Fully Automated Solid-Phase Microwave-Assisted cGMP-Ready Process for the Preparation of Eptifibatide
| العنوان: | An Optimized Scalable Fully Automated Solid-Phase Microwave-Assisted cGMP-Ready Process for the Preparation of Eptifibatide |
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| المؤلفون: | L. Pacini, Annunziata D’Ercole, Matteo Zini, Alfredo Paio, Paolo Rovero, Anna Maria Papini, Giuseppina Sabatino, Arianna Ribecai |
| المصدر: | Organic process research & development (2021). doi:10.1021/acs.oprd.0c00490 info:cnr-pdr/source/autori:Papini, Anna Maria; Sabatino, Giuseppina; D'Ercole, Annunziata; Pacini, Lorenzo; Zini, Matteo; Ribecai, Arianna; Paio, Alfredo; Rovero, Paolo/titolo:An optimized scalable fully automated solid-phase microwave-assisted cGMP-ready process for the preparation of eptifibatide/doi:10.1021%2Facs.oprd.0c00490/rivista:Organic process research & development/anno:2021/pagina_da:/pagina_a:/intervallo_pagine:/volume |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Materials science, Scale-up, Nanotechnology, active pharmaceutical ingredient, peptide, scale-up, oxidation, automated on-resin disulfide bond formation, off-resin disulfide bond formation, single reactor solid-phase synthesis, 010402 general chemistry, 01 natural sciences, Microwave assisted, chemistry.chemical_compound, Phase (matter), Oxidation, medicine, Peptide synthesis, Physical and Theoretical Chemistry, Active ingredient, 010405 organic chemistry, Organic Chemistry, Off-resin disulfide bond formation, 0104 chemical sciences, Fully automated, chemistry, Scientific method, Peptide, Single reactor solid-phase synthesis, Scalability, Eptifibatide, Active pharmaceutical ingredient, Automated on-resin disulfide bond formation, medicine.drug |
| الوصف: | We investigated several strategies, based on the use of microwave-assisted solid-phase peptide synthesis (MW-SPPS) and scalable to kilogram-scale manufacturing, for the preparation of Eptifibatide, a disulfide-bridged cyclo-heptapeptide drug approved as an antithrombotic agent. Following the very fast microwave-assisted Fmoc/tBu synthesis of the linear precursor, we explored both the solution (off-resin) and the solid-phase (on-resin) disulfide formation. In order to optimize the oxidation in solution, we focused our attention on the mild disulfide formation procedure based on the use of air, observing some drawbacks, such as the formation of unwanted oxidation byproducts, such as dimers, or the use of large volumes of an environmentally unfriendly solvent (CHCN). In order to overcome these difficulties, we studied four different on-resin strategies, with the final aim to develop a fully automated, single reactor procedure, exploring different strategies to protect the thiol side-chain functional group on the C-terminal Cys residue and to form the Eptifibatide ring. The main difference among these strategies is represented by the final cyclization mode that was obtained either by direct formation of an S-S disulfide bridge or by head to MPA on cysteine side-chain amide bond formation. In conclusion, the optimization of the latter strategy enabled us to devise an optimized scalable fully automated solid-phase microwave-assisted cGMP-ready process to prepare Eptifibatide. |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::87c4b0fe2aba17e3983bfb82d507cdb0 http://hdl.handle.net/2158/1219739 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....87c4b0fe2aba17e3983bfb82d507cdb0 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |