Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College , Huazhong University of Science and Technology , Wuhan 430030 , People's Republic of China.
School of Chemistry and Pharmaceutical Engineering , Taishan Medical University , Tai-An 271016 , People's Republic of China.
J Nat Prod. 2018 Dec 28;81(12):2673-2681. doi: 10.1021/acs.jnatprod.8b00490. Epub 2018 Nov 19.
Thirteen new grayanane diterpenoid glucosides, 3- epi-grayanoside B (1), micranthanosides A-E (2-6), 7α-hydroxygrayanoside C (7), micranthanoside F (8), 14β-acetyoxymicranthanoside F (9), micranthanoside G (10), 14- O-acetylmicranthanoside G (11), 14β-hydroxypieroside A (12), and micranthanoside H (13), and six known analogues (14-19) were isolated from the leaves of Rhododendron micranthum. The structures of 1-19 were elucidated based on spectroscopic analysis, comparison with literature, and chemical methods. The absolute configurations of 3- epi-grayanoside B (1) and micranthanosides A (2) and C (4) were defined by single-crystal X-ray diffraction analysis. This is the first report of the crystal structures of grayanane diterpenoid glucosides. 3- epi-Grayanoside B (1) represents the first example of a 3α-oxygrayanane diterpenoid glucoside, and micranthanosides A-D (2-5) are the first examples of 5α-hydroxy-1-β H-grayanane diterpenoids. In addition, micranthanosides C-F (4-6 and 8) and 14β-acetyoxymicranthanoside F (9) represent the first examples of grayanane glucosides with the glucosylation at C-16. All the grayanane diterpenoid glucosides 1-19 were assayed for their anti-inflammatory, antitumor, and PTP1B inhibitory activities, but did not show significant activities at 40 μM. Grayanane diterpenoid glucosides 1-18 were evaluated for their antinociceptive activity, and compounds 2, 3, 7-10, 12, 13, and 16 showed significant antinociceptive effects with percentage inhibitions in excess of 50%.
从密叶碎米花（Rhododendron micranthum）的叶子中分离得到了 13 个新的灰杨烷二萜糖苷，包括 3-表灰杨苷 B（1）、密叶碎米花苷 A-E（2-6）、7α-羟基灰杨苷 C（7）、密叶碎米花苷 F（8）、14β-乙酰氧基密叶碎米花苷 F（9）、密叶碎米花苷 G（10）、14-O-乙酰基密叶碎米花苷 G（11）、14β-羟基贝壳杉苷 A（12）和密叶碎米花苷 H（13），以及 6 个已知类似物（14-19）。基于光谱分析、文献比较和化学方法，确定了 1-19 的结构。通过单晶 X 射线衍射分析确定了 3-表灰杨苷 B（1）和密叶碎米花苷 A（2）和 C（4）的绝对构型。这是首次报道灰杨烷二萜糖苷的晶体结构。3-表灰杨苷 B（1）代表第一个 3α-氧基灰杨烷二萜糖苷，密叶碎米花苷 A-D（2-5）代表第一个 5α-羟基-1-βH-灰杨烷二萜。此外，密叶碎米花苷 C-F（4-6 和 8）和 14β-乙酰氧基密叶碎米花苷 F（9）代表第一个 C-16 位葡萄糖化的灰杨苷。所有灰杨烷二萜糖苷 1-19 均进行了抗炎、抗肿瘤和 PTP1B 抑制活性测试，但在 40μM 时没有表现出显著活性。评价了灰杨烷二萜糖苷 1-18 的镇痛活性，化合物 2、3、7-10、12、13 和 16 具有超过 50%的抑制百分比，表现出显著的镇痛作用。
