Process development with Bifunctional chiral epoxides to access single enantiomrs of pharmaceutical intermediates

Masaya Ikunaka, Takeshi Sugai

Research output: Contribution to journalArticle

Abstract

Two selected case studies on process development will be discussed; one is on the enantiocontrolled synthesis of (S)-3-hydroxytetradecanoic acid (2), an intermediate of ONO-4007 (3) processing anti-Tnmour activity, which employs double homologation of (S)-epichlorohydrin (ECH) (1b) with its ter mini being differentiated The other is on the enantioselective access to N-4-cyano-3-Trifluoromethyiphenyl-(S)-2,3-dihydroxy-2-methylpropananmide (5a), an intermediate of (R)-bicultamide (5b) exhibiting potent anti-Androgen activity, which starts with enantioconvergent preparation Of (R)-3-benzyloxy-2-methylpropane-1,2-diol (4) from O-benzyl (±)-2- methylglycidol (1c) by the enantiocomplementary hydroxysis using Bacillus subtilis epoxide hydrolase (BSEH) and H2SO4 in sequence. In each case study, emphasis will be placed on how to select viable synthetic routes on the basis of availability of single anantiomers of chiral starting materials and preparative methods thereof. In the chemoenzymatic synthesis of (S)-5a, BSEH indispensable for building its quatermary stereogenic center is developed from scratch, which culminates in successful overexpression of its gene from B. subtilis JCM 10629 under the infuence of an amylase promother and terminator of B. amyloliquefaciens NBRC 15535 in an engineered strain of B. subtilis MT-2 deficient in neutral protease. The discussion should help to develop process chemistry in producing value-Added fine chemicals from glycerol, one of its natural sources being plam oil.

Original languageEnglish
Pages (from-to)143-158
Number of pages16
JournalJournal of Oil Palm Research
Issue numberSPEC. ISS. OCTOBE
Publication statusPublished - 2008 Oct

Fingerprint

Epoxide Hydrolases
Hydrolases
Epoxy Compounds
Bacilli
Bacillus subtilis
epoxides
Drug products
Epichlorohydrin
epoxide hydrolase
drugs
Amylases
Glycerol
Pharmaceutical Preparations
Androgens
Oils
Peptide Hydrolases
Genes
Availability
case studies
glycols

Keywords

  • (R)-3-Benzyloxy-2-methylpropane-1-2-diol
  • (S)-3-hydroxytetradecanioc acid-N-4-cyano-3-Trifluoromethylphenyl(S)-2
  • (S)-Epichlorohydrin
  • 3-dihydroxy-2-methylpropanamide
  • Epoxide hydrolase-Palm oil
  • Glycerol

ASJC Scopus subject areas

  • Agronomy and Crop Science
  • Food Science
  • Renewable Energy, Sustainability and the Environment
  • Biomaterials

Cite this

Process development with Bifunctional chiral epoxides to access single enantiomrs of pharmaceutical intermediates. / Ikunaka, Masaya; Sugai, Takeshi.

In: Journal of Oil Palm Research, No. SPEC. ISS. OCTOBE, 10.2008, p. 143-158.

Research output: Contribution to journalArticle

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