Time Economy in Total Synthesis
Time Economy in Total Synthesis
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DOI：
10.1021/acs.joc.0c01581
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发表时间：
2021-01-01
影响因子：
3.6
通讯作者：
Hayashi, Yujiro
中科院分区：
文献类型：
--
作者：
Hayashi, Yujiro
人们常说“时间就是金钱”。在多步合成中，当迫切需要高价值产品或一组产品时，这当然是正确的。满足这一需求需要合理地平衡原子经济性、步骤经济性和氧化还原经济性与制造产品所花费的时间。在这个以流感为基础的大流行时代，迅速提供有效治疗药物的必要性使得“节省时间”的重要性尤为明显。在这个角度来看，时间经济在全合成的重要性，以及强调所需分子的及时生产的一般考虑。作为案例研究，达菲，科里内酯，布洛芬的合成进行了讨论，重点是比较经典和当代的方法快速全合成。通过使用现代战术，如一锅反应程序和通用的合成方法，如有机催化剂介导的多米诺反应加上严格控制的技术，如流动化学，达菲和科里内酯现在可以分别在60和152分钟内合成，使用一个容器通过分批系统。达菲和布洛芬可以通过流动系统制备，它们的总停留时间分别为11.5和3 min。
It is often said that "time is money". This is certainly true in a multistep synthesis when a high-valued product or set of products is needed urgently. Fulfilling this need requires the sensible balancing of atom economy, step economy, and redox economy with the time taken to make the product. In this age of flu-based pandemics, the need for rapid provision of effective therapeutic agents makes the importance of "time economy" particularly clear. In this Perspective, the importance of time economy in total synthesis is described, as well as the general considerations underlining the timely production of desired molecules. As case studies, the syntheses of Tamiflu, Corey lactone, and ibuprofen are discussed, with emphasis on comparing classical and contemporary approaches to a rapid total synthesis. By using modern tactics such as one-pot reaction procedures and versatile synthetic methodologies such as organocatalyst mediated domino reactions coupled with strict-control technologies such as flow chemistry, Tamiflu and Corey lactone can now be synthesized within 60 and 152 min, respectively, using one vessel via a batch system. Tamiflu and ibuprofen can be prepared via flow system, and their total residence times are 11.5 and 3 min, respectively.