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Synthesis and Liver Microsomal Metabolic Stability Studies of a Fluorine‐Substituted δ‐Tocotrienol Derivative
Author(s) -
Liu Xingui,
Poddar Saikat,
Song Lin,
Hendrickson Howard,
Zhang Xuan,
Yuan Yaxia,
Zhou Daohong,
Zheng Guangrong
Publication year - 2020
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201900676
Subject(s) - derivative (finance) , allylic rearrangement , hydrolysis , chemistry , microsome , tocotrienol , double bond , stereochemistry , metabolic stability , in vitro , organic chemistry , biochemistry , antioxidant , tocopherol , catalysis , vitamin e , financial economics , economics
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.