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Synthesis of (2R,8' S,3' E)-?-tocodienol, a tocoflexol family member designed to have a superior pharmacokinetic profile compared to ?-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)-?-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 compound 1 utilizing naturally-occurring ?-tocotrienol as a starting material (24% total yield). The key step in the synthesis is oxidative olefin cleavage of ?-tocotrienol to afford the chroman core of 1 with retention of chirality at the C-2 stereocenter.

SUBMITTER: Liu X

PROVIDER: S-EPMC5070675 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Synthesis of (2R,8' S,3' E)-δ-tocodienol, a tocoflexol family member designed to have a superior pharmacokinetic profile compared to δ-tocotrienol.

Liu Xingui X Gujarathi Satheesh S Zhang Xuan X Shao Lijian L Boerma Marjan M Compadre Cesar M CM Crooks Peter A PA Hauer-Jensen Martin M Zhou Daohong D Zheng Guangrong G

Tetrahedron 20160512 27-28

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 compound 1 utilizing naturally-occurring δ-tocotrienol as a starting material (24% total yield ...[more]

PMID: 27773949

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