Balancing skeleton and functional groups in total syntheses of complex natural products: a case study of tigliane, daphnane and ingenane diterpenoids

• Published in: Natural product reports 2021-09, Vol.38 (9), p.1589-1617
• Main Authors: Liu, Zhi, Ding†, Zhengwei, Chen, Kai, Xu, Ming, Yu, Tao, Tong, Guanghu, Zhang, Hailong, Li, Pengfei
• Format: Article
• Language: English
• Subjects: Biological Products - chemistry; Diterpenes; Diterpenes - chemistry; Functional groups; Industrial applications; Natural products
• ISSN: 0265-0568; 1460-4752
• DOI: 10.1039/d0np00086h

Total synthesis of natural products has greatly contributed to natural product research, organic synthesis and drug discovery and development. However, in most cases, the efficiency of total synthesis is far from sufficient for direct practical industrial application. Thus, designing a concise and efficient synthetic route with balanced efforts between building the complex skeleton and introducing functional groups is highly desirable. In this critical review, we first present an introduction of this issue and a philosophical framework that cover possible synthetic approaches. Next, we have chosen the biogenetically closely related, biologically important and synthetically extremely challenging natural products, tiglianes, daphnanes and ingenanes as the particular case for the discussion, since in the past 40 years many synthetic approaches have been reported. The successes and pitfalls included therefore serve as the basis to draw some conclusions that may inspire future development in this area. The fruitful advancement in synthetic chemistry of the title families of complex diterpenes has stimulated and enjoyed strategic balance between building the skeletons and installing the functional groups.