Synthesis of Natural Product‐like Indeno[2,1‐b]indole/Shikimic Acid Hybrid Analogues with Anti‐osteoclastogenic Activity via Photo‐Nazarov Reaction

Abstract

AbstractIndeno[2,1‐b]indole and shikimic acid‐like structures are natural privileged scaffolds in several bioactive NPs. In this work, we developed a high‐efficient and diastereoselective synthetic approach to construct novel indeno[2,1‐b]indole/shikimic acid hybrid analogues via photo‐Nazarov reaction. The protocol is the first case of excited‐state photo‐Nazarov cyclization of indole‐2‐yl vinyl ketone to indeno[2,1‐b]indole. (6aS, 10aR)‐products were afforded in moderate to good yields (37–92 %) for most of substrates (91 % for model substrate 1 aa) after the condition optimization. Even more attractive, several synthesized analogues (2 t, 3 c and 3 d) exhibited potent RANKL‐induced osteoclastogenesis inhibitory activities (inhibitory rate >50 % at 5 μM), which suggested promising prospect of the novel tetracyclic indeno[2,1‐b]indole/shikimic acid hybrid scaffold for anti‐osteoporosis drug development.