Investigation on the epoxidation of piperitenone, and structure-activity relationships of piperitenone oxide for differentiation-inducing activity

Ryohei Sato, Azusa Sasaki, Yuko Mori, Mio Komai, Shogo Kamo, Mai Onuki, Takafumi Seki, Zen Kawabe, Shu Miyajima, Shusuke Tomoshige, Tsuneomi Kawasaki, Shuichi Sato, Takako Nakamura, Nakao Kubo, Seiji Takeda, Shuichi Date, Shigehisa Okamoto, Panida Boonyaritthongchai, Krit Thirapanmethee, Mullika Traidej ChomnawangBhanubong Bongcheewin, Thuy Linh Nguyen, Huong Lan Thi Nguyen, Huong Thi Le, Yasushi Nakamura, Kouji Kuramochi

Research output: Contribution to journalArticlepeer-review

Abstract

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 by1H 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.

Original languageEnglish
Pages (from-to)951-958
Number of pages8
JournalJournal of oleo science
Volume69
Issue number8
DOIs
Publication statusPublished - 2020

Keywords

  • Differentiation-inducing activity
  • Piperitenone
  • Piperitenone oxide
  • Structure-activity relationships

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

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