(±)-Homocrepidine A, a Pair of Anti-inflammatory Enantiomeric Octahydroindolizine Alkaloid Dimers from Dendrobium crepidatum
Yang Hu, Chaofeng Zhang, Xin Zhao, Yue Wang, Deqiang Feng, Mian Zhang, Haifeng Xie
Journal of Natural Products
A pair of racemic indolizidine enantiomers, (±)-homocrepidine A (1), and a piperidine derivative, homocrepidine B (2), were isolated from Dendrobium crepidatum along with the known alkaloid crepidine (3). The racemic mixture of 1 was separated into a pair of enantiomers, (+)-1 and (−)-1, by HPLC using a chiral chromatographic substrate, which represents the first successful example of resolving indolizidine racemic mixtures. The absolute configurations of (+)-1 and (−)-1 were assigned from single-crystal X-ray diffraction data. The evaluation of anti-inflammatory activity with LPS-induced RAW 264.7 macrophages revealed that (+)-1 strongly inhibited the production of nitric oxide (IC50, 3.6 μM) and significantly decreased the expression of inducible nitric oxide synthase, while (−)-1 and (±)-1 only had moderate inhibitory effects (IC50, 22.8 and 14.7 μM). Compound 2 showed moderate anti-inflammatory activity (IC50, 27.6 μM).
Circular dichroism, Absolute configuration, Natural products