Cyclohexane-Fused Octahydroquinolizine Alkaloids from Myrioneuron faberi with Activity against Hepatitis C Virus

Investigation of the alkaloids from Myrioneuron faberi, a plant unique to China, gave four pairs of enantiomers (1-4). (+/-)-beta-Myrifabral A (1) and (+/-)-alpha-myrifabral A (2) formed an inseparable mixture of anomers (duster A), as did (+/-)-beta-myrifabral B (3) and (+/-)-alpha-myrifabral B (4) (cluster B). Their structures were determined by X-ray diffraction and NMR analysis. Compounds 1-4 possessed novel cyclohexane-fused octahydroquinolizine skeletons and represent the first quinolizidine alkaloids from the genus Myrioneuron. The epimers of cluster A (1 and 2) were modified and separated. In vitro, clusters A and B and their derivatives inhibited replication of hepatitis C virus (HCV, IC50 0.9 to 4.7 mu M) with cytotoxicity lower than that of telaprevir.