Hou Yongsheng, Shi Tao, Yang Yuhang, Fan Xiaohong, Chen Jinhong, Cao Fei, Wang Zhen
School of Pharmacy , Lanzhou University , West Donggang Road No. 199 , Lanzhou 730000 , Gansu , China.
State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering , Lanzhou University , Lanzhou 730000 , Gansu , China.
Org Lett. 2019 Apr 19;21(8):2952-2956. doi: 10.1021/acs.orglett.9b01042. Epub 2019 Apr 11.
The first asymmetric total syntheses of tuberostemoamide, sessilifoliamide A, and their epimers have been accomplished via the common intermediate ethylstemoamide. The stereochemistry control relationship at C8/C9/C10 of ethylstemoamide is clearly revealed for the first time, and a subtle difference of substituent at the C10 position between stemoamide and ethylstemoamide (Me vs Et) drastically changes the stereoselectivity, which is significantly valuable for syntheses of ethylstemoamide structurally related Stemona alkaloids. Biological studies reveal that the activities of each epimer show a significant difference. 11,13-Bis- epi-sessilifoliamide A is expected to be a selective and reversible BChE inhibitor for the treatment of neurodegenerative diseases, and sessilifoliamide A may be a part of the anti-inflammatory substances in Stemonaceae plants.
通过共同中间体乙基百部酰胺，首次完成了对节茎百部酰胺、轮叶百部酰胺A及其差向异构体的首次不对称全合成。首次明确揭示了乙基百部酰胺在C8/C9/C10处的立体化学控制关系，并且百部酰胺和乙基百部酰胺在C10位取代基的细微差异（甲基对乙基）极大地改变了立体选择性，这对于合成与乙基百部酰胺结构相关的百部生物碱具有重要价值。生物学研究表明，每种差向异构体的活性存在显著差异。11,13-双表轮叶百部酰胺A有望成为一种用于治疗神经退行性疾病的选择性和可逆性胆碱酯酶抑制剂，而轮叶百部酰胺A可能是百部科植物中抗炎物质的一部分。
