Currently, pyripyropene A, which is isolated from the culture broth of Aspergillus fumigatus FO‐1289, is the only compound known to strongly and selectively inhibit the isozyme sterol O‐acyltransferase 2 (SOAT2). To aid in the development of new cholesterol‐lowering or anti‐atherosclerotic agents, new A‐ring simplified pyripyropene A analogues have been designed and synthesized based on total synthesis, and the results of structure–activity relationship studies of pyripyropene A. Among the analogues, two A‐ring simplified pyripyropene A analogues exhibited equally efficient SOAT2 inhibitory activity to that of natural pyripyropene A. These new analogues are the most potent and selective SOAT2 inhibitors to be used as synthetic compounds and attractive seed compounds for the development of drug for dyslipidemia, including atherosclerotic disease and steatosis.

中文翻译：

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作为有效和选择性合成 SOAT2 抑制剂的 A 环简化 Pyripyropene A 类似物的设计和合成


目前，从烟曲霉FO-1289 培养液中分离出来的吡啶平 A 是唯一已知能强烈、选择性抑制同工酶甾醇O酰基转移酶 2 (SOAT2) 的化合物。为了帮助开发新型降胆固醇或抗动脉粥样硬化药物，基于全合成以及吡咯平A的构效关系研究结果，设计并合成了新的A环简化吡咯平A类似物。 ，两个A环简化pyripyropene A类似物表现出与天然pyripyropene A同等有效的SOAT2抑制活性。这些新类似物是最有效和选择性的SOAT2抑制剂，可用作合成化合物和有吸引力的种子化合物，用于血脂异常药物的开发，包括动脉粥样硬化疾病和脂肪变性。