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.

Keywords Plus: VINYLOGOUS ALDOL REACTION，EFFICIENT TOTAL-SYNTHESIS，CHINESE CRUDE DRUG，APOPTOSIS，INCISUM，DIENE

Published in ORGANIC LETTERS，Volume28；10.1021/acs.orglett.6c02393，JUL 2026