目的 对苗药金丝梅Hypericum patulum中的𠮿酮类化学成分进行分离和结构鉴定，并评价化合物对α-葡萄糖苷酶的抑制活性。方法 采用多种色谱技术进行分离纯化，通过红外、高分辨质谱、核磁共振和电子圆二色谱等分析方法鉴定化合物的结构，采用PNPG法测定α-葡萄糖苷酶抑制活性。结果 从金丝梅中分离鉴定16个𠮿酮衍生物化合物，分别为 (R)-1,3,5-三羟基-4-[5-甲基-2-(丙-1-烯-2-基)己-4-烯-1-基]-9H-呫吨-9-酮（1）、1,3,5-三羟基-4-[(2R,4S)-4-羟基-5-甲基-2-(丙-1-烯-2-基)己-5-烯-1-基]-9H-呫吨-9-酮（2）、(R,E)-1,3,5-三羟基-4-[5-羟基-5-甲基-2-(丙-1-烯-2-基)己-3-烯-1-基]-9H-呫吨-9-酮（3）、(R)-4-(2,6-二甲基-3-甲基烯基庚-5-烯-1-基)-1,3,7-三羟基-9H-呫吨-9-酮（4）、ugaxanthone（5）、6-去氧异巴西红厚壳素（6）、toxyloxanthone B（7）、5,8-羟基-2,2-二甲基-2H,6H-吡啶(3,2-b)氧杂蒽-6-酮（8）、1,6-二羟基-5-甲氧基-6',6'-二甲基-2H-吡喃[2', 3':3, 2]𠮿酮（9）、1-羟基-7-甲氧基𠮿酮（10）、2-甲氧基𠮿酮（11）、5-羟基-2-甲氧基𠮿酮（12）、2-羟基𠮿酮（13）、1,7-羟基-4-甲氧基𠮿酮（14）、2,3,4-三甲氧基𠮿酮（15）、2,3-二甲氧基𠮿酮（16），其中化合物1～4为新化合物。6个化合物（2、3、5、7、8和12）具有良好的α-葡萄糖苷酶抑制活性，半数抑制浓度（median inhibition concentration，IC₅₀）为（0.13±0.02）～（74.89±0.56）μg/mL。其中化合物5 [IC₅₀＝（0.13±0.02）μg/mL] 表现出最显著的α-葡萄糖苷酶抑制活性，其IC₅₀是阳性对照阿卡波糖[IC₅₀＝（162.09±2.84）μg/mL]的1 200倍。结论 从苗药金丝梅中分离得到16个𠮿酮类化合物，化合物1～4为新化合物，分别命名为金丝梅𠮿酮A（1）、金丝梅𠮿酮B（2）、金丝梅𠮿酮C（3）和金丝梅𠮿酮D（4）。化合物8、9、11和14首次在金丝桃属植物中分离得到，化合物5、6、10、12、13、15和16首次在金丝梅植物中分离得到。体外实验结果表明，侧链上的羟基可以提高其抑制活性。丰富了𠮿酮的结构多样性，同时也为糖尿病的治疗提供了先导化合物。

Objective To isolate and identify the xanthone derivatives in Hypericum patulum, and evaluate the inhibitory activity of the compounds on α-glucosidase. Methods A variety of chromatographic techniques were applied for the chemical separation and purification. Their structures were elucidated by a combination of IR, HR-ESI-MS, NMR, and ECD spectra. PNPG method was performed to evaluate the α-glucosidase inhibitory activity. Results Sixteen xanthone derivatives (1—16) were isolated from H. patulum, namely, (R)-1,3,5-trihydroxy-4-[5-methyl-2-(prop-1-en-2-yl)hex-4-en-1-yl]-9H-xanthen-9-one (1), 1,3,5-trihydroxy-4-[(2R,4S)-4-hydroxy-5-methyl-2-(prop-1-en-2-yl)hex-5-en-1-yl]-9H-xanthen-9-one (2), (R,E)-1,3,5-trihydroxy-4-[5-hydroxy-5-methyl-2-(prop-1-en-2-yl)hex-3-en-1-yl]-9H-xanthen-9-one (3), (R)-4-(2,6-dimethyl-3-methylidenehept-5-en-1-yl)-1,3,7-trihydroxy-9H-xanthen-9-one (4), ugaxanthone (5), 6-deoxyisojacareubin (6), toxyloxanthone B (7), 5,8-dihydroxy-2,2-dimethyl-2H,6H-pyrano (3, 2-b) xanthen-6-one (8), 1,6-dihydroxy-5-methoxy-6',6'-dimethyl-2H-pyrano[2',3':3,2]xanthone (9), 1-hydroxy-7-methoxyxanthone (10), 2-methoxyxanthone (11), 5-hydroxy-2-methoxyxanthone (12), 2-hydroxyxanthone (13), 1,7-dihydroxy-4-methoxyxanthone (14), 2,3,4-trimethoxyxanthone (15) and 2,3-dimethoxyxanthone (16). Among them, four new compounds (1—4) were identified. Six compounds (2, 3, 5, 7, 8, and 12) exhibited good α-glucosidase inhibitory activity, with IC₅₀ values ranging from (0.13 ±0.02) μg/mL to (74.89 ±0.56) μg/mL. Compound 5 [IC₅₀ = (0.13 ±0.02) μg/mL] showed the most potential α-glucosidase inhibitory activity, which was about 1 200 times stronger than the positive control, acarbose [IC₅₀ = (162.09 ±2.84) μg/mL]. Conclusion Sixteen xanthones, including four new compounds are isolated from H. patulum. Four new compounds were named as patulumone A (1), patulumone B (2), patulumone C (3), and patulumone D (4). Compounds 8, 9, 11, and 14 are isolated from Hypericum plants for the first time, and compounds 5, 6, 10, 12, 13, 15, and 16 are isolated from H. patulum for the first time. The results of in vitro experiments showed that the hydroxyl groups on the side chain could improve its inhibitory activity. It can enrich the structural diversity of xanthone and provide lead compounds for the treatment of diabetes.

R284.1

国家自然科学基金面上项目（32270413）；贵州省科技创新人才团队（黔科合平台人才-CXTD[2022]007）