Chemo-enzymatic synthesis of (R,R)-(-)-Pyrenophorin

Takeshi Sugai, Osamu Katoh, Hiromichi Ohta

Research output: Contribution to journalArticle

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Abstract

A chemo-enzymatic approach to (R,R)-(-)-pyrenophorin starting from commercially available 6-methyl-5-hepten-2-one is described. Firstly, (R)-6-methyl-5-hepten-2-ol (sulcatol) was prepared by interface-bioreactor mediated asymmetric reduction of the corresponding ketone by a yeast, Pichia farinosa IAM 4682 (51% yield, 90%e.e.). The sequential carbon-chain elongation via Horner-Emmons olefination of protected aldehyde and cyanation afforded all of carbon skeleton in the seco acid with a desired β,γ-(E)-double bond. By the aid of a microorganism, Rhodococcus rhodochrous IFO15564, the nitrile was efficiently hydrolyzed to give the corresponding carboxylic acid, (R,E)-7-hydroxy-3-octenoate, the key synthetic intermediate without affecting the position and configuration of the double bond (90% yield). Dimeric lactone structure was obtained by utilizing a lipase-catalyzed lactonization. While Pseudomonas cepacia lipase-catalyzed reaction worked in a moderate efficiency, higher yield of desired dimeric lactone (44%) was obtained by the use of an immobilized form of Candida antarctica lipase. The lactonization was accelerated in the presence of molecular sieves 4A. (R,R)-(-)-Pyrenophorin was obtained from this dimeric lactone (Seebach's intermediate) by the subsequent chemical transformation.

Original languageEnglish
Pages (from-to)11987-11998
Number of pages12
JournalTetrahedron
Volume51
Issue number44
DOIs
Publication statusPublished - 1995 Oct 30

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Lactones
Lipase
Carbon
Burkholderia cepacia
Rhodococcus
Nitriles
Pichia
Candida
Molecular sieves
Bioreactors
Carboxylic Acids
Ketones
Skeleton
Aldehydes
Microorganisms
Yeast
Elongation
Yeasts
Acids
pyrenophorin

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

Chemo-enzymatic synthesis of (R,R)-(-)-Pyrenophorin. / Sugai, Takeshi; Katoh, Osamu; Ohta, Hiromichi.

In: Tetrahedron, Vol. 51, No. 44, 30.10.1995, p. 11987-11998.

Research output: Contribution to journalArticle

Sugai, Takeshi ; Katoh, Osamu ; Ohta, Hiromichi. / Chemo-enzymatic synthesis of (R,R)-(-)-Pyrenophorin. In: Tetrahedron. 1995 ; Vol. 51, No. 44. pp. 11987-11998.
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