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

• Published in: Journal of organic chemistry 2014-09, Vol.79 (17), p.7945-7950
• Main Authors: Cao, Ming-Ming, Zhang, Yu, Li, Xiao-Hui, Peng, Zong-Gen, Jiang, Jian-Dong, Gu, Yu-Cheng, Di, Ying-Tong, Li, Xiao-Nian, Chen, Duo-Zhi, Xia, Cheng-Feng, He, Hong-Ping, Li, Shun-Lin, Hao, Xiao-Jiang
• Format: Article
• Language: English
• Subjects: Alkaloids - chemistry; Alkaloids - isolation & purification; Alkaloids - pharmacology; Antiviral Agents - chemistry; Antiviral Agents - isolation & purification; Antiviral Agents - pharmacology; Crystallography, X-Ray; Cyclohexanes - chemistry; Cyclohexanes - isolation & purification; Cyclohexanes - pharmacology; Hepacivirus - drug effects; Heterocyclic Compounds, 4 or More Rings - chemistry; Heterocyclic Compounds, 4 or More Rings - isolation & purification; Heterocyclic Compounds, 4 or More Rings - pharmacology; Humans; Magnetic Resonance Spectroscopy; Molecular Structure; Quinolizines - chemistry; Quinolizines - isolation & purification; Quinolizines - pharmacology; Stereoisomerism
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo501076x

Investigation of the alkaloids from Myrioneuron faberi, a plant unique to China, gave four pairs of enantiomers (1–4). (±)-β-Myrifabral A (1) and (±)-α-myrifabral A (2) formed an inseparable mixture of anomers (cluster A), as did (±)-β-myrifabral B (3) and (±)-α-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 μM) with cytotoxicity lower than that of telaprevir.