title: Synthesis of (13) C2 (15) N2 -labeled anti-inflammatory and cytoprotective tricyclic bis(cyanoenone) ([(13) C2 (15) N2 ]-TBE-31) as an internal standard for quantification by stable isotope dilution LC-MS method.
abstract: Tricyclic bis(cyanoenone), TBE-31, one of the most potent activators of the Keap1/Nrf2/antioxidant response element pathway, has been developed as a new anti-inflammatory and cytoprotective agent. (13) C2 (15) N2 -labeled TBE-31 ([(13) C2 (15) N2 ]-TBE-31), which has two (13) C and two (15) N atoms in two cyano groups, was designed to develop a method for quantification of cell, tissue, and plasma levels of TBE-31 that involves chromatography/mass spectrometry coupled with the use of a stable isotope-labeled internal standard. [(13) C2 (15) N2 ]-TBE-31 was successfully synthesized in four steps from a previously reported intermediate, which is prepared in 11 steps from cyclohexanone, by introduction of two (13) C atoms with ethyl [(13) C]formate and two (15) N atoms with hydroxyl[(15) N]amine. The stable isotope dilution liquid chromatography-mass spectrometry method for quantification of TBE-31 was successfully developed using [(13) C2 (15) N2 ]-TBE-31 to compensate for any variables encountered during sample processing and analysis.
authors.affiliation: Institute of Chemical Biology and Drug Discovery, Stony Brook University, Stony Brook, NY, 11794, USA.
authors.forename: Suqing
authors.initials: S
authors.lastname: Zheng
authors.forename: Jeffrey T-J
authors.initials: JT
authors.lastname: Huang
authors.forename: Elena V
authors.initials: EV
authors.lastname: Knatko
authors.forename: Sheila
authors.initials: S
authors.lastname: Sharp
authors.forename: Maureen
authors.initials: M
authors.lastname: Higgins
authors.forename: Iwao
authors.initials: I
authors.lastname: Ojima
authors.forename: Albena T
authors.initials: AT
authors.lastname: Dinkova-Kostova
authors.forename: Tadashi
authors.initials: T
authors.lastname: Honda
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D002247:Carbon Isotopes / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid / Q000592:standards; D013058:Mass Spectrometry / Q000592:standards; D051379:Mice; D009590:Nitrogen Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D010616:Phenanthrenes / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011865:Radioisotope Dilution Technique / Q000592:standards; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D012015:Reference Standards
chemical_list: D000893:Anti-Inflammatory Agents; D002247:Carbon Isotopes; D009590:Nitrogen Radioisotopes; D010616:Phenanthrenes; D019275:Radiopharmaceuticals; C531972:TBE 31
keywords: Keap1/Nrf2/ARE activator; anti-inflammatory; carbon-13; cytoprotective; isotopically labeled synthesis; nitrogen-15; stable isotope dilution LC-MS method