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

Xingui Liu, Satheesh Gujarathi, Xuan Zhang, Lijian Shao, Marjan Boerma, Cesar M. Compadre, Peter A. Crooks, Martin Hauer-Jensen, Daohong Zhou, Guangrong Zheng

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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)-δ-Tocodienol (1) was predicted to be a high value tocoflexol for further pharmacological evaluation. We now report here an efficient eight-step synthetic route to compound 1 utilizing 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 of 1 with retention of chirality at the C-2 stereocenter.

Original languageEnglish (US)
Pages (from-to)4001-4006
Number of pages6
JournalTetrahedron
Volume72
Issue number27-28
DOIs
StatePublished - 2016
Externally publishedYes

Keywords

  • C–C coupling
  • Desulfonylation
  • Oxidative olefin cleavage
  • Tocodienol
  • Tocotrienol

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Synthesis of (2R,8′S,3′E)-δ-tocodienol, a tocoflexol family member designed to have a superior pharmacokinetic profile compared to δ-tocotrienol'. Together they form a unique fingerprint.

Cite this