分子設計と有機合成による高機能型生物活性分子の創製：Physalin類のかご型構造の合成と生物機能

抄録

We have focused on the design and creation of new biologically active molecules based on natural products or biomolecules. This article summarizes our synthetic approach towards the clarification of the mode-of-action of physalins, which are complex oxygenated steroidal natural products. Physalins consist of the typical plant-steroidal structure displayed in the AB-ring and the unique cage-shaped DEFGH-ring system present on the right side of the structures. As other plants steroids such as withanolides possess a similar AB-ring structure and sometimes exhibit similar biological activities, the AB-ring structure was considered to be relevant for their biological functions. We synthesized physalin analogues without the AB-ring structure in order to clarify the contribution of the right-side cage-shaped structure for the biological effect in physalins. Biological investigations using the synthesized analogues along with the natural products revealed that, among the analogues, PBright-4 showed moderate inhibitory activity towards NF-κB transcriptional activation, through a similar mode-of-action with physalin B, which possesses a double bond at the C5-C6 position. These results clearly indicated that the right-side partial structure of physalins plays a significant role in their biological activity.