目的 研究黑桑Morus nigra茎枝中新颖的Diels-Alder型加合物，并初步评价其过氧化物酶体增殖物激活受体γ（peroxisome proliferator-activated receptor gamma，PPARγ）结合活性。方法 采用硅胶、AB-8大孔吸附树脂、聚酰胺、Sephadex LH-20凝胶及ODS反相柱色谱等多种方法进行系统分离纯化；通过高分辨质谱（HR-ESI-MS）、核磁共振波谱（¹H-NMR、¹³C-NMR）等现代波谱技术对所得单体化合物进行结构鉴定，通过PPARγ配体结合实验对部分化合物进行体外活性考察。结果 从黑桑茎枝乙醇提取物中分离得到6个Diels-Alder型加合物，分别鉴定为 (5aR,10aR,14S)-2-((1S,2R,3S)-2-(2,4-二羟基苯甲酰)-2′,4′-二羟基-5-甲基-1,2,3,6-四氢-[1,1′-联苯基]-3-基)-1,3,8,14-四羟基-13,13-二甲基-11H-10a,5a-(环氧丙基桥)苯并呋喃并[3,2-b]色烯-11-酮（1）、桑根酮O（2）、桑根酮C（3）、桑呋喃F（4）、cathayanin B（5）、桑呋喃G（6）。化合物1在10 μmol/L浓度下对PPARγ显示出微弱的配体结合活性；化合物3在10 μmol/L浓度下对PPARγ具有一定的配体结合活性，但明显弱于其生源前体sanggenol F。结论 化合物1为新的Diels-Alder加合物，命名为黑桑根酮Q，该化合物由1分子桑根酮型二氢黄酮与1分子查耳酮经[4＋2]环加成生成，C-2位异戊烯基侧链氧化后与C-3位通过氧桥形成六元环，最终构建出结构新颖的[4,4,3]桥环体系。化合物3具有一定的PPARγ配体结合活性。

Objective Novel Diels-Alder-type adducts from the stems and branches of Morus nigra were investigated, and their peroxisome proliferator-activated receptor gamma (PPARγ) binding activity was preliminarily evaluated. Methods Systematic isolation and purification were carried out by multiple chromatographic methods including silica gel, AB-8 macroporous resin, polyamide, Sephadex LH-20 gel and ODS reversed-phase column chromatography. Structures of the isolated compounds were identified by modern spectroscopic techniques including high-resolution electrospray ionization mass spectrometry（HR-ESI-MS）and nuclear magnetic resonance spectroscopy (¹H-NMR, ¹³C-NMR). The in vitro activities of some compounds were evaluated by PPARγ ligand-binding assay. Results Six Diels-Alder adducts were isolated from the ethanol extract of M. nigra twigs and identified as (5aR,10aR,14S)-2-((1S,2R,3S)-2-(2,4-dihydroxybenzoyl)-2',4'-dihydroxy-5-methyl-1,2,3,6-tetrahydro-[1,1'-biphenyl]-3-yl)-1,3,8, 14-tetrahydroxy-13,13- dimethyl-11H-10a,5a-(epoxypropano)benzofuro[3,2-b]chromen-11-one (1), sanggenon O (2), sanggenon C (3), mulberrofuran F (4), cathayanin B (5), and mulberrofuran G (6). Compound 1 exhibited weak PPARγ ligand-binding activity at 10 μmol/L. Compound 3 exhibited moderate ligand-binding activity toward PPARγ at 10 μmol/L, which was obviously weaker than that of its biosynthetic precursor sanggenol F (SGF). Conclusion Compound 1 is a new compound, named nigragenon Q, it is formed by an intermolecular [4+2] cycloaddition between a sanggenone-type dihydroflavone and a chalcone. Oxidation of the C-2 isoprenyl side chain enables its connection to C-3 via an oxygen bridge, furnishing a six-membered ring and constructing a unique [4,4,3] bridged ring system. Compound 3 exhibited moderate PPARγ ligand-binding activity.

R284.1

国家自然科学基金资助项目（32270421）