Alstolarines A and B, two unusual monoterpenoid indole alkaloids with an acetal moiety from Alstonia scholaris

Abstract

Two novel monoterpenoid indole alkaloids, alstolarines A and B (1–2), were isolated from the leaves and twigs of Alstonia scholaris. Compound 1 is the first vobasinyl-type alkaloid with a 6/5/8/5/6/5 hexacyclic architecture featuring an unprecedented 21-oxa-4-azaspiro[4,4]nonane unit. Compound 2 is the first 21-nor-vobasinyl-type alkaloid with a unique 3-oxa-4-azatricyclo[5.1.1.1^3,20]undecane ring system. Their structures including absolute configurations were established by a combination of spectroscopic data analyses, electronic circular dichroism (ECD) calculations, and single crystal X-ray diffraction analysis. The plausible biogenetic pathways of 1 and 2 were also proposed. Compounds 1 and 2 exhibited promising vasorelaxant activities with EC₅₀ values of 4.6 and 6.7 μM, and compound 2 showed moderate acetylcholinesterase (AChE) inhibitory activity with an IC₅₀ value of 19.3 μM.