Four-step continuous-flow total synthesis of (-)-debromoflustramine B using a chiral heterogeneous Pd NP catalyst

• Published in: Chemical science (Cambridge) Vol. 15; no. 39; pp. 16205 - 16209
• Main Authors: Wang, Junwen, Liang, Feng, Dong, Zhen, Huang, Junrong, Zhu, Yuxiang, You, Hengzhi, Chen, Fen-Er
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 09.09.2024; The Royal Society of Chemistry
• Subjects: Addition polymerization; Alkaloids; Biological activity; Catalysts; Chemical synthesis; Chemistry; Continuous flow; Natural products; Palladium; Tryptophan
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d4sc03471f

Various prenylated indoline alkaloids with diverse biological activities, including (-)-debromoflustramine B with significant butyrylcholinesterase inhibitory activity, could be synthesized by dearomative prenylation reactions of tryptophan derivatives. However, previously reported dearomative prenylations were limited to batch reactions at the milligram scale, requiring multistep reactions and complex post-processing to obtain the desired natural products. The more efficient synthesis of alkaloids remains challenging, as does the recovery of expensive catalysts. Herein, we developed a chiral heterogeneous Pd nanoparticle (NP) catalyst supported on a polymer, which produces indoline alkaloids in high yields with excellent enantioselectivities. Additionally, the first gram-scale four-step continuous-flow total synthesis of (-)-debromoflustramine B was successfully achieved with this chiral Pd heterogeneous catalyst, requiring only a simple post-processing step.