Chirotechnology: Designing Economic Chiral Syntheses
Chirotechnology: Designing Economic Chiral Syntheses
复制标题
手性技术：设计经济的手性合成
DOI：
10.1002/chin.199701319
复制
发表时间：
1997
期刊：
影响因子：
--
通讯作者：
R. Sheldon
中科院分区：
文献类型：
--
作者：
R. Sheldon
随着人们对手性在生物活性方面重要性的认识不断提高，对工业上合成纯对映体的有效方法的需求不断增长。综述了合成纯对映体的各种方法，即利用手性池、通过结晶技术或酶动力学拆分分离外消旋体以及催化不对称合成，并对这些方法进行了比较。影响工艺经济性的因素，因此，路线选择进行了讨论。特别是催化不对称合成与动力学拆分的优点和局限性划定。阐述了关于经济手性合成设计的一般准则，并通过参考商业上重要的手性药物（例如氨苄西林和阿莫西林侧链、萘普生和布洛芬、卡托普利和地尔硫卓）的生产进行说明。鉴于成本效益技术的快速增长，对映体纯形式的手性药物的工业合成显然是一个经济可行的主张。此外，了解所涉及的一般原则为确定最有吸引力的过程提供了坚实的基础。
The increasing awareness of the importance of chirality in the context of biological activity has stimulated a growing demand for efficient methods for the industrial synthesis of pure enantiomers. Various methodologies for the synthesis of pure enantiomers, viz. use of the chiral pool, separation of racemates via crystallization techniques or enzymatic kinetic resolution and catalytic asymmetric synthesis are reviewed and compared. Factors which influence the process economics and, hence, route selection are discussed. In particular the merits and limitations of catalytic asymmetric synthesis versus kinetic resolution are delineated. General guidelines are elaborated regarding the design of economic chiral syntheses and are illustrated by reference to the manufacture of commercially important chiral drugs, e.g. ampicillin and amoxycillin side‐chains, naproxen and ibuprofen, captopril and diltiazem. Given the rapidly growing repertoire of cost‐effective technologies, the industrial synthesis of chiral pharmaceuticals in enantiomerically pure form is clearly an economically viable proposition. Moreover, as understanding of the general principles involved provides a sound basis for identifying the most attractive process.