Chemoenzymatic synthesis of (2S,3S,4S)-form, the physiologically active stereoisomer of dehydroxymethylepoxyquinomicin (DHMEQ), a potent inhibitor on NF-κB

Manabu Hamada, Yukihiro Niitsu, Chihiro Hiraoka, Ikuko Kozawa, Toshinori Higashi, Mitsuru Shoji, Kazuo Umezawa, Takeshi Sugai

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

A new route for (2S,3S,4S)-form, the physiologically active stereoisomer of dehydroxymethylepoxyquinomicin (DHMEQ), a potent NF-κB inhibitor, was established by chemoenzymatic approach. Elaboration on the asymmetric epoxidation of a p-benzoquinone monoketal with benzylcinchonidinium tert-butylhydroperoxide yielded an epoxyenone, in 79.8% ee and 57% yield in reproducible manner. By way of the transformation of this key intermediate to enantiomerically pure (2S,3S,4S)-DHMEQ, the contaminating undesired enantiomer could be effectively removed by applying Burkholderia cepacia lipase-catalyzed hydrolysis of diacylated precursor. The above integrated combination of chemical asymmetric synthesis and enzyme-catalyzed kinetic resolution enabled us to prepare active DHMEQ in a large-scale.

Original languageEnglish
Pages (from-to)7083-7087
Number of pages5
JournalTetrahedron
Volume66
Issue number35
DOIs
Publication statusPublished - 2010 Aug 28

Fingerprint

Stereoisomerism
Burkholderia cepacia
tert-Butylhydroperoxide
Enzyme kinetics
Epoxidation
Enantiomers
Lipase
Hydrolysis
Enzymes
dehydroxymethylepoxyquinomicin

Keywords

  • Asymmetric epoxidation
  • DHMEQ
  • Hydrolysis
  • Kinetic resolution
  • Lipase

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

Chemoenzymatic synthesis of (2S,3S,4S)-form, the physiologically active stereoisomer of dehydroxymethylepoxyquinomicin (DHMEQ), a potent inhibitor on NF-κB. / Hamada, Manabu; Niitsu, Yukihiro; Hiraoka, Chihiro; Kozawa, Ikuko; Higashi, Toshinori; Shoji, Mitsuru; Umezawa, Kazuo; Sugai, Takeshi.

In: Tetrahedron, Vol. 66, No. 35, 28.08.2010, p. 7083-7087.

Research output: Contribution to journalArticle

Hamada, Manabu ; Niitsu, Yukihiro ; Hiraoka, Chihiro ; Kozawa, Ikuko ; Higashi, Toshinori ; Shoji, Mitsuru ; Umezawa, Kazuo ; Sugai, Takeshi. / Chemoenzymatic synthesis of (2S,3S,4S)-form, the physiologically active stereoisomer of dehydroxymethylepoxyquinomicin (DHMEQ), a potent inhibitor on NF-κB. In: Tetrahedron. 2010 ; Vol. 66, No. 35. pp. 7083-7087.
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