Global Green Chemistry Metrics Analysis Algorithm and Spreadsheets: Evaluation of the Material Efficiency Performances of Synthesis Plans for Oseltamivir Phosphate (Tamiflu) as a Test Case
Global Green Chemistry Metrics Analysis Algorithm and Spreadsheets: Evaluation of the Material Efficiency Performances of Synthesis Plans for Oseltamivir Phosphate (Tamiflu) as a Test Case
复制标题
DOI：
10.1021/op800157z
复制
发表时间：
2009-03-01
影响因子：
3.4
通讯作者：
Andraos, John
中科院分区：
文献类型：
--
作者：
Andraos, John
这项工作公开了一种简单易用的算法，可以根据绿色度量标准来评估任何类型的合成计划的全局材料效率性能，而不考虑给定目标分子的复杂性。该算法具有较强的鲁棒性，已用于Excel电子表格的快速计算和数值结果的图形化。为了证明这一特殊工具在过程和合成化学家对合成性能的评估和评级中的易用性，已经研究了用于治疗H5N1流感病毒的神经氨酸酶抑制剂磷酸奥司他韦的各种合成计划。特别是，从核心和全球反应质量效率和E因子、原子经济性和总产率性能等方面对6个工业合成和9个学术小组的方案进行了全面和严格的评价。此外，所有已报道的方案都根据新的合成优雅参数进行了评估，包括牺牲试剂的相对分子质量、催化性(氧化水平)指数和每个反应步骤的目标键数。介绍了目标结构键合图和轮廓，作为直观、简洁地描述合成策略的方便方法。这些强大的算法和可视化辅助工具可以用来立即发现综合计划中的瓶颈。此外，它们允许对合成计划进行更深入的理解和批评，从而帮助化学家为进一步优化提出新的方向。
This work discloses an easy-to-use algorithm to evaluate the global material efficiency performance of any kind of synthesis plan regardless of complexity to a given target molecule according to green metrics criteria. The algorithm is robust and has been adapted to Excel spreadsheets for rapid calculation and graphing of the numerical results. In order to demonstrate the facile utility of this exceptional tool for process and synthetic chemists in the evaluation and ranking of synthetic performance, various Synthesis plans for oseltamivir phosphate, a neuraminidase inhibitor used to treat the H5N1 influenza virus, have been investigated. In particular, six industrial syntheses and nine plans from academic groups have been thoroughly and rigorously evaluated according to kernel and global reaction mass efficiencies and E-factors, atom economy, and overall yield performances. In addition, all reported plans were evaluated according to new synthesis elegance parameters including friction of sacrificial reagents by molecular weight, hypsicity (oxidation level) index, and number (it target bonds made per reaction step. Target structure bond maps and profiles are introduced as convenient ways to visually describe synthetic strategy compactly. These powerful algorithms and visual aids can he used to immediately spot bottlenecks in a Synthesis plan. Moreover, they allow deeper understanding and critiquing of synthesis plans, thereby assisting chemists in suggesting new directions for further optimization.