Total synthesis of natural products containing bicyclo[n.2.2] ring systems

Bridged bicyclo[m.n.2] ring systems (m >2, n >= 2) are important structural scaffolds, which are widely found in diverse families of natural products. Such natural products are attracting increasing research interests because of their intriguing architectural features and significant biological activities. However, the total synthesis of natural products containing a bridged bicyclo[m.n.2] ring system has proved to be very challenging because there are few efficient approaches to this unique structural motif. In this Minireview, seven representative types of natural products with bridged bicyclo[n.2.2] ring systems are discussed. For each example, we focus on the synthetic routes and highlight the methods and strategies used to prepare bridged bicyclo[n.2.2] ring systems. Lastly, a summary and outlook as well as a discussion of the key features of each strategy applied in the total syntheses are presented. This review demonstrates the creativity and diversity during the synthetic designs of bicyclo[m.n.2] ring systems.