Progress in the synthesis of polycyclic natural products

Steroid natural products often act as signal molecules in vivo, so they have important physiological activities A small number of members of this family have broken skeleton structure, which is called secosteroids Their chemical synthesis and biological activities have not attracted enough attention In 2015, the kigoshi research group of Tsukuba University reported the separation of aplysiasecosterol a (angel Chem Int ed 2015, 547073) from Aplysia kurodai The natural content of the compound is very rare, but it has a special chemical structure: the parent nucleus of tricyclic diketone connects the highly substituted cyclopentane side chain through a carbon carbon single bond, and eight consecutive chiral centers in the molecule pose a certain challenge to chemical synthesis Li Ang group of Shanghai Institute of organic chemistry, Chinese Academy of Sciences recently completed the total synthesis of a series of polycyclic natural products (angelw Chem Int ed 2018, 57952; J am Chem SOC 20181404227; J am Chem SOC 20181409025) Recently, Lu Zhaohong, Zhang Xiang and Guo Zhicong of the group completed the first total synthesis of aplysiasecosterol a (J am Chem SOC 20181409211) Based on the implied symmetry of the molecular structure, they constructed the all carbon quaternary carbon chiral center of the left fragment with the strategy of desymmetrization, and formed a rigid tricyclic structure through the free radical cyclization; using Aggarwal lithium boration and Zweifel Evans alkylation, they quickly prepared the right fragment containing the continuous tertiary carbon chiral center The connection of the two fragments is based on the reformatsky type reaction developed by Oshima et al And then the conjugated ketene intermediate is obtained by dehydration The key step in the later stage of synthesis is the free radical cyclization initiated by hydrogen atom transfer Three consecutive all carbon chiral centers are formed in one step with high cyclization efficiency and stereoselectivity The longest linear sequence of this synthesis route is only 14 steps This research was supported by the strategic leading science and technology program of the Chinese Academy of Sciences (category B), NSFC science foundation for Distinguished Young Scholars, and innovative research groups.