Work

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

Year: 2024

Type: article

Abstract: Indeno[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. (6a S , 10a R )‐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 μ M), which suggested promising prospect of the novel tetracyclic indeno[2,1‐ b ]indole/shikimic acid hybrid scaffold for anti‐osteoporosis drug development.

Source: European Journal of Organic Chemistry

DOI: 10.1002/ejoc.202400933