title: Synthesis of (2R,8'S,3'E)-δ-tocodienol, a tocoflexol family member designed to have a superior pharmacokinetic profile compared to δ-tocotrienol.
abstract: A group of side chain partially saturated tocotrienol analogues, namely tocoflexols, have been previously designed in an effort to improve the pharmacokinetic properties of tocotrienols. (2R,8'S,3'E,11'E)-δ-Tocodienol (1) was predicted to be a high value tocoflexol for further pharmacological evaluation. We now report here an efficient 8-step synthetic route to compound1utilizing naturally-occurring δ-tocotrienol as a starting material (24% total yield). The key step in the synthesis is oxidative olefin cleavage of δ-tocotrienol to afford the chroman core of1with retention of chirality at the C-2 stereocenter.
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
authors: Xingui
authors: X
authors: Liu
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
authors: Satheesh
authors: S
authors: Gujarathi
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
authors: Xuan
authors: X
authors: Zhang
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
authors: Lijian
authors: L
authors: Shao
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
authors: Marjan
authors: M
authors: Boerma
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
authors: Cesar M
authors: CM
authors: Compadre
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
authors: Peter A
authors: PA
authors: Crooks
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
authors: Martin
authors: M
authors: Hauer-Jensen
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
authors: Daohong
authors: D
authors: Zhou
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
authors: Guangrong
authors: G
authors: Zheng
keywords: C-C coupling; Desulfonylation; Oxidative olefin cleavage; Tocodienol; Tocotrienol