Annotinolide F and lycoannotines A-I, further Lycopodium alkaloids from Lycopodium annotinum.

Seven lycopodine-type (annotinolide F and lycoannotines A-F), two lycodine-type (lycoannotines G and H), and one fawcettimine-type (lycoannotine I) previously undescribed naturally occurring Lycopodium alkaloids together with thirteen known ones were isolated from the whole plant of Lycopodium annotinum. Their structures and absolute configurations were determined by extensive spectroscopic methods, single-crystal X-ray diffraction, chemical transformation, and electronic circular dichroism (ECD) calculations. Among the isolates, annotinolide F, lycoannotines A and B are unusual 7,8-seco-lycopodane derivatives, and annotinolide F even further possesses a rare 8,5-lactone framework through a lactonization after the C-7/C-8 bond cleavage. Lycoannotine C is an uncommon 8,15-seco lycopodine-type alkaloid, whereas lycoannotine I represents the first example of a naturally occurring C-9/N bond cleavage product of fawcettimine-type alkaloid. Among them, only lycoannotine I was found to show considerable anti-butyrylcholinesterase (anti-BuChE) activity.