Asymmetric Total Synthesis and Antihypoxic Neuroinflammatory Evaluation of Notopterol, Notoptol, and Their Natural
Yongsheng Hou1, Jiaqi Liu1,2, Xingrong Wang1
1CAS Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Lanzhou 730000, People's Republic of China.
Abstract:
The first asymmetric total synthesis of bioactive furocoumarins notopterol (1), notoptol (8), and nine natural analogues is reported. It features a gram-scale, BTHL-catalyzed asymmetric vinylogous-Mukaiyama-aldol reaction (VMAR) with excellent enantioselectivity (>98% ee). A subsequent 1,3-rearrangement converts notopterol (1) to notoptol (8), suggesting a plausible biosynthetic relationship. This work represents the first application of the BTHL catalytic system to non-Brassard diene substrates. Biological evaluation identified (-)-1 and (-)-3 as potent, configuration-dependent antihypoxic neuroinflammatory agents, highlighting the value of the synthesis.
