Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Acad. Kuprevicha Str. 5/2, 220141 Minsk, Belarus.
Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Acad. Kuprevicha Str. 5/2, 220141 Minsk, Belarus.
Steroids. 2019 Jul;147:62-69. doi: 10.1016/j.steroids.2018.10.001. Epub 2018 Oct 5.
A series of novel fluorine-containing lupane triterpenoid acid derivatives with fluoroaromatic amide moieties at the C-28 position (1-8) or with 2-(fluoroacyl)cyclopentane-1,3-dione fragments at the C-3 position (9-18) of lupane skeleton was synthesized. A simple synthesis of novel lupane triterpenoid hybrids with 2-(fluoroacyl)-2-cyclopenten-1-one moieties was developed. An interaction of 2-acyl-3-chlorocyclopent-2-en-1-ones, obtained from corresponding cyclic β-triketones, with methyl 3-amino-3-deoxybetulinate gave 3β-isomers (9-13) and 3α-isomers (14-18) of target hybrids, which were isolated as individual compounds. Anti-inflammatory properties of selected synthesized compounds were studied in vivo using the histamine-, concanavalin A- and sheep erythrocytes immunization-induced mouse paw edema models. The antioxidant activity was investigated in vivo on the model of tetracycline-induced hepatitis. Majority of synthesized fluorine-containing lupane triterpenoid acid derivatives exhibited significant anti-inflammatory and antioxidant effects. Among studied compounds, 3β-hybrid 11 with 2-perfluorobutanoyl-2-cyclopenten-1-one moiety was the most potent bioactive compound.
合成了一系列新型含氟甾体皂角苷酸衍生物，其在甾体骨架的 C-28 位具有氟芳酰胺部分（1-8）或在 C-3 位具有 2-（氟代酰基）环戊烷-1,3-二酮片段（9-18）。开发了一种新型含氟甾体皂角苷杂合体的简单合成方法，其中具有 2-（氟代酰基）-2-环戊烯-1-酮部分。从相应的环状β-三酮获得的 2-酰基-3-氯环戊-2-烯-1-酮与 3-氨基-3-去氧白桦脂酸甲酯反应，得到目标杂合体的 3β-异构体（9-13）和 3α-异构体（14-18），它们作为单个化合物被分离出来。使用组胺、刀豆球蛋白 A 和绵羊红细胞免疫诱导的小鼠爪肿胀模型在体内研究了选定合成化合物的抗炎特性。在四环素诱导的肝炎模型中研究了抗氧化活性。大多数合成的含氟甾体皂角苷酸衍生物表现出显著的抗炎和抗氧化作用。在所研究的化合物中，具有 2-全氟丁酰基-2-环戊烯-1-酮部分的 3β-杂合体 11 是最有效的生物活性化合物。
