(+)-/(−)-Ormohenins A and B, two pairs of ormosanine-type enantiomers and their derivatives with neuroprotective activity from Ormosia henryi Prain

Abstract

Two pairs of undescribed alkaloid enantiomers, (+)-/(−)-ormohenins A (1) and B (2), were isolated from the seeds of Ormosia henryi Prain, along with four undescribed alkaloids (3, 4, 7 and 8) and seven known ones (5, 6, 9–13). Compounds 1–6 belong to the ormosanine-type alkaloids, compounds 7, 9, and 11 are of the lupinine-type, compounds 8 and 10 are classified as anagyrine-type alkaloids, 12 and 13 are cytisine-type alkaloids. The chemical structures of 1–13 were elucidated through comprehensive NMR and MS data analyses. Furthermore, the racemates (±)-1 and (±)-2 were successfully resolved into their respective optically pure enantiomers using a chiral HPLC system. The absolute configurations of compounds 1–3 were determined using single-crystal X-ray diffraction and corroborated by DFT calculations of specific rotations. The absolute configurations of 4, 7, and 8 were assigned by the experimental electronic circular dichroism (ECD) with those predicted using TDDFT calculations. Compound 12 exhibited significant acetylcholinesterase (AChE) inhibitory activity with the IC₅₀ value of 6.581 ± 1.203 μM. The neuroprotective effects of these compounds against Aβ_25-35 induced cell damage in PC12 cells were investigated, and compounds 3, 9, and 12 exhibited significant neuroprotective effects against Aβ_25-35 induced PC12 cell damage, with the EC₅₀ values of 7.99–15.49 μM, respectively.

Graphical Abstract