Xu Mingming, Di Di, Fan Lu, Ma Yingrun, Wei Xinyi, Shang Er-Xin, Onakpa Monday M, Johnson Oluwatosin O, Duan Jin-Ao, Che Chun-Tao, Zhou Junfei, Zhao Ming
Jiangsu Collaborative Innovation Centre of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resource Industrialization and Formulae Innovative Medicine, Key Laboratory of Chinese Medicinal Resource Recycling Utilization Under National Administration of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, School of Pharmacy, Nanjing, Jiangsu, 210023, People's Republic of China.
School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People's Republic of China.
Phytochemistry. 2023 Oct;214:113804. doi: 10.1016/j.phytochem.2023.113804. Epub 2023 Aug 2.
Thirteen previously undescribed (9β-H)-pimarane derivatives, icacinolides A-G (1-7) and oliviformislactones C-H (8-13), together with four known analogs (14-17), were isolated from the leaves of Icacina oliviformis. Their structures were constructed by extensive spectroscopic analysis, C NMR-DP4+ analysis, ECD calculation, single-crystal X-ray diffraction, and chemical methods. These structurally diverse isolates were classified into six framework types: rearranged 3-epi-17-nor-(9β-H)-pimarane, rearranged 17-nor-(9β-H)-pimarane, 16-nor-(9β-H)-pimarane, 17-nor-(9β-H)-pimarane, 17,19-di-nor-(9β-H)-pimarane, and (9β-H)-pimarane. Among them, compounds 1, 5, and 7 were the first examples of three rearranged 3-epi-17-nor-(9β-H)-pimaranes featuring a unique (11S)-carboxyl-9-oxatricyclo[5.3.1.0]dodecane motif with contiguous stereogenic centers, whereas their C-3 epimers, compounds 2-4 and 6 were the second examples of four rearranged 17-nor-(9β-H)-pimaranes. Additionally, compounds 8 and 12/13 represented the second examples of a 16-nor-(9β-H)-pimarane and two 17,19-di-nor-(9β-H)-pimaranes, respectively. In cytotoxic bioassay, compound 2 exhibited significant cytotoxic against HT-29 with IC values of 7.88 μM, even stronger than 5-fluorouracil, and 15 showed broad-spectrum cytotoxic activities against HepG2, HT-29, and MIA PaCa-2 with IC values of 11.62, 9.77, and 4.91 μM, respectively. Meanwhile, a preliminary structure-activity relationship suggested that 3,20-epoxy, 6,19-lactone, 2-OH, 7-OH, and 8-OH in (9β-H)-pimarane derivatives might be active groups, whereas ring C aromatization may decrease the cytotoxic activities.
从橄榄叶滨藜的叶子中分离出13种先前未描述的(9β-H)-海松烷衍生物，即滨藜内酯A-G（1-7）和橄榄叶内酯C-H（8-13），以及4种已知类似物（14-17）。它们的结构通过广泛的光谱分析、碳核磁共振- DP4+分析、电子圆二色计算、单晶X射线衍射和化学方法确定。这些结构多样的分离物被分为六种骨架类型：重排的3-表-17-降-(9β-H)-海松烷、重排的17-降-(9β-H)-海松烷、16-降-(9β-H)-海松烷、17-降-(9β-H)-海松烷、17,19-二降-(9β-H)-海松烷和(9β-H)-海松烷。其中，化合物1、5和7是三种重排的3-表-17-降-(9β-H)-海松烷的首个实例，其具有独特的(11S)-羧基-9-氧杂三环[5.3.1.0]十二烷基序且带有相邻的手性中心，而它们的C-3差向异构体，即化合物2-4和6是四种重排的17-降-(9β-H)-海松烷的第二个实例。此外，化合物8和12/13分别代表16-降-(9β-H)-海松烷和两种17,19-二降-(9β-H)-海松烷的第二个实例。在细胞毒性生物测定中，化合物2对HT-29表现出显著的细胞毒性，IC值为7.88 μM，甚至强于5-氟尿嘧啶，化合物15对HepG2、HT-29和MIA PaCa-2表现出广谱细胞毒性活性，IC值分别为11.62、9.77和4.91 μM。同时，初步的构效关系表明，(9β-H)-海松烷衍生物中的3,20-环氧、6,19-内酯、2-OH、7-OH和8-OH可能是活性基团，而环C芳构化可能会降低细胞毒性活性。
