Divergent sustainability profiles of molnupiravir synthesis routes are governed by solvent use and process design

• 成果类型: Article
• 署名作者: Chen, Zhengyun; Lian, Justin Z.; Huang, Haozhou; Zhu, Hengyi; Kanye, Lynda Thubelihle; Chen, Mateng; Zhang, Zhihao; Liu, Boxin; Zhang, Jiawei; Ahmed, Ajaz; Barbarossa, Valerio; Cucurachi, Stefano; Dong, Bin
• 署名单位: China Pharmaceutical University; Leiden University; Leiden University - Excl LUMC; New York University; China Pharmaceutical University; China Pharmaceutical University; Imperial College London; University of California System; University of California Los Angeles; China Pharmaceutical University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8426
• DOI: 10.1073/pnas.2502336122
• 发表日期: 2025-09-18
• 关键词: life-cycle assessment; scale-up; candidate; chemistry; eidd-2801; batch

摘要

This study presents a comparative cradle-to-gate environmental and economic evaluation of nine synthetic routes for Molnupiravir (EIDD-2801), a broad-spectrum antiviral drug. Integrating Life Cycle Assessment (LCA) with Life Cycle Costing (LCC), we quantified the environmental impacts alongside capital and operational costs, net present costs, and break-even prices of each route. The results reveal significant variation across the schemes, with Schemes #1 and #2 exhibiting the highest impacts and costs due to intensive use of chloroform and diethyl ether, while Scheme #8 demonstrated the lowest impacts and costs, benefitting from higher batch output, greener solvents, and process intensification. Scenario analyses showed that solvent recovery improves sustainability onlywhen high recovery rates are combined with clean electricity; otherwise, the additional energy demand may offset benefits. Scale-up analysis confirmed that higher production scales substantially reduce per-gram impacts and costs, supporting economies of scale. These findings highlight the critical role of solvent management, energy sourcing, the use of sustainability assessment at the earliest stages of innovation, and process design in aligning green chemistry with economic viability. The proposed integrated LCA-LCC framework provides transferable insights to guide sustainable pharmaceutical manufacturing and supports the development of evidence-based policy for greener antiviral drug production.