Piperitenone oxide, a major chemical constituent of the essential oil of spearmint, Mentha spicata, induces differentiation in human colon cancer RCM-1 cells. In this study, piperitenone oxide and trans-piperitenone dioxide were prepared as racemic forms by epoxidation of piperitenone. The relative configuration between two epoxides in piperitenone dioxide was determined to be trans by ¹H NMR analysis and nuclear Overhauser effect spectroscopy (NOESY) in conjunction with density functional theory (DFT) calculations. Optical resolution of (±)-piperitenone oxide by high-performance liquid chromatography (HPLC) using a chiral stationary phase (CSP) afforded both enantiomers with over 98% enantiomeric excess (ee). Evaluation of the differentiation-inducing activity of the synthetic compounds revealed that the epoxide at C-1 and C-6 in piperitenone oxide is important for the activity, and (+)-piperitenone oxide has stronger activity than (–)-piperitenone oxide. The results obtained in this study provide new information on the application of piperitenone oxide and spearmint for differentiation-inducing therapy. Furthermore, natural piperitenone oxide was isolated from M. spicata. The enantiomeric excess of the isolated natural piperitenone oxide was 66% ee. Epoxidation of piperitenone with hydrogen peroxide proceeded in a phosphate buffer under weak basic conditions to give (±)-piperitenone oxide. These results suggest that the nonenzymatic epoxidation of piperitenone, which causes a decrease in the enantiomeric excess of natural piperitenone oxide, is accompanied by an enzymatic epoxidation in the biosynthesis of piperitenone oxide.

氧化胡椒薄荷，留兰香，精油的主要化学成分留兰香，诱导分化人结肠癌RCM-1细胞。在这项研究中，通过哌啶酮的环氧化将哌啶酮氧化物和反式哌啶酮二氧化物制备为外消旋形式。通过¹ H NMR分析和核Overhauser效应光谱法（NOESY）结合密度泛函理论（DFT）计算，确定二氧化哌啶酮中两个环氧化物之间的相对构型是反式的。使用手性固定相（CSP）通过高效液相色谱（HPLC）拆分（±）-哌啶酮氧化物的光学拆分，两种对映体的对映体过量均超过98％（ee）。对合成化合物的诱导分化活性的评估表明，哌啶酮氧化物中C-1和C-6处的环氧化物对该活性很重要，并且（+）-哌啶酮氧化物的活性比（-）-哌啶酮氧化物强。在这项研究中获得的结果提供了关于氧化胡椒酮和留兰香在诱导分化治疗中的应用的新信息。此外，自然氧化胡椒从分离M.兰香。分离出的天然哌啶酮氧化物的对映体过量为ee的66％。在弱碱性条件下，在磷酸盐缓冲液中用过氧化氢进行哌啶酮的环氧化，得到（±）-哌啶酮氧化物。这些结果表明，引起天然哌啶酮氧化物的对映体过量的减少的哌啶酮的非酶促环氧化伴随着哌啶酮氧化物的生物合成中的酶促环氧化。