Synthesis and Liver Microsomal Metabolic Stability Studies of a Fluorine-Substituted δ-Tocotrienol Derivative

Xingui Liu, Saikat Poddar, Lin Song, Howard Hendrickson, Xuan Zhang, Yaxia Yuan, Daohong Zhou, Guangrong Zheng

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

A fluoro-substituted δ-tocotrienol derivative, DT3-F2, was synthesized. This compound was designed to stabilize the metabolically labile terminal methyl groups of δ-tocotrienol by replacing one C−H bond on each of the two methyl groups with a C−F bond. However, in vitro metabolic stability studies using mouse liver microsomes revealed an unexpected rapid enzymatic C−F bond hydrolysis of DT3-F2. To the best of our knowledge, this is the first report of an unusual metabolic hydrolysis of allylic C−F bonds.

Original languageEnglish (US)
Pages (from-to)506-516
Number of pages11
JournalChemMedChem
Volume15
Issue number6
DOIs
StatePublished - Mar 18 2020
Externally publishedYes

Keywords

  • C−F bond hydrolysis
  • fluorination
  • metabolic stability
  • synthesis
  • tocotrienol

ASJC Scopus subject areas

  • Drug Discovery
  • General Pharmacology, Toxicology and Pharmaceutics
  • Molecular Medicine
  • Biochemistry
  • Pharmacology
  • Organic Chemistry

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