Department of Chemistry, Graduate School of Science, Tohoku University, 6-3 Aramaki Aza Aoba, Aoba-ku, Sendai 980-8578, Japan.
J Org Chem. 2021 Jan 1;86(1):1-23. doi: 10.1021/acs.joc.0c01581. Epub 2020 Oct 21.
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.
常言说得好,“时间就是金钱”。当需要急需高附加值产品或产品组合时,这句话在多步合成中确实如此。满足这一需求需要明智地平衡原子经济性、步骤经济性和氧化还原经济性与生产产品所需的时间。在这个流感大流行的时代,快速提供有效治疗剂的需求使得“时间经济性”的重要性尤为明显。在本观点中,描述了时间经济性在全合成中的重要性,以及强调适时生产所需分子的一般考虑因素。作为案例研究,讨论了达菲、Corey 内酯和布洛芬的合成,重点比较了快速全合成的经典和现代方法。通过使用一锅反应程序等现代策略以及有机催化剂介导的多米诺反应等多功能合成方法,并结合流化学等严格控制技术,现在可以通过批处理系统在一个容器中分别在 60 和 152 分钟内合成达菲和 Corey 内酯。可以通过流系统制备达菲和布洛芬,它们的总停留时间分别为 11.5 和 3 分钟。