Asymmetric synthesis and biological activities of natural product (+)-balasubramide and its derivatives
Asymmetric synthesis and biological activities of natural product (+)-balasubramide and its derivatives
复制标题
天然产物()-巴拉舒布胺及其衍生物的不对称合成及生物活性
DOI：
10.1080/14786419.2015.1071363
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发表时间：
2016-04-02
影响因子：
2.2
通讯作者：
Lin, Hansen
中科院分区：
文献类型：
--
作者：
Li, Jun;Li, Jianzu;Lin, Hansen
采用两步不对称合成法合成了天然产物（+）-巴拉舒布酰胺（3 j）及其衍生物（3a-3 i），并测定了3a-3 j的体外生物活性。选择（2S，3R）-（+）-3-苯基环氧乙烷-2-羧酸甲酯（1h）作为起始原料，其不对称合成方法已在前面的文献中描述过。评价化合物3a-3 j的神经保护、抗氧化和抗神经炎症作用。（+）-巴拉舒布酰胺及其在6-苯环上具有不同电负性基团的衍生物几乎不产生神经保护和抗氧化作用，但在BV-2小胶质细胞中诱导了有效的抗神经炎症作用（3g除外）。化合物3c在其6-苯基环中具有三氟甲基，是特别有效的抗神经炎剂。这些结果表明，（+）-巴拉舒布酰胺的6-苯环的电负性是其抑制神经炎症作用的重要决定因素。更多的电负性取代基导致更有效的抗神经炎症作用。此外，细胞毒性测定表明测试化合物没有显著影响。
The natural product (+)-balasubramide (3j) and its derivatives (3a-3i) were synthesized using a two-step asymmetric synthesis, and the biological activities of 3a-3j were determined in vitro. Methyl (2S,3R)-(+)-3-phenyloxirane-2-carboxylate (1h), the asymmetric synthesis of which was described in a previous paper, was selected as the starting material. Compounds 3a-3j were evaluated for their neuroprotective, antioxidative, and anti-neuroinflammatory effects. (+)-Balasubramide and its derivatives with different electronegative groups in the 6-phenyl ring produced little neuroprotection and antioxidation, but induced potent anti-neuroinflammatory effects in BV-2 microglial cells (with the exception of 3g). Compound 3c, with a trifluoromethyl group in its 6-phenyl ring, was a particularly potent anti-neuroinflammatory agent. These results demonstrated that the electronegativity of the 6-phenyl ring of (+)-balasubramide is an important determinant of its inhibitory effect on neuroinflammation. More electronegative substituents result in more potent anti-neuroinflammatory effects. Moreover, cytotoxicity assays indicated no significant effects of the tested compounds.