Enzyme-catalyzed resolution of 3,8-dioxatricyclo[3.2.1.02,4]octane-6-carboxylic esters and the application to the synthesis of 3-epishikimic acid

Manabu Hamada, Yoshikazu Inami, Yasuhito Nagai, Toshinori Higashi, Mitsuru Shoji, Seiichiro Ogawa, Kazuo Umezawa, Takeshi Sugai

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

3,8-Dioxatricyclo[3.2.1.02,4]octane-6-carboxylic acid, whose racemic form is readily available on a large scale, is a versatile starting material for the synthesis of carbasugars and carbocyclic biologically active natural products. In this study, the enzyme-catalyzed kinetic resolution was attempted on a variety of corresponding carboxylic esters. The hydrophobic and hydrophilic properties of ester substituents greatly affected the rate of reaction and the enantioselectivity. Hydrolysis of the corresponding 2′-chloroethyl ester with pig liver esterase worked well in a highly enantioselective manner (E = 116) to give the hydrolyzate (90.6% ee) and unreacted ester recovery (99.4% ee). The hydrolyzate is a precursor for (-)-oseltamivir phosphate, and a route to (3S,4S,5R)-(-)-3-epishikimic acid was developed from the recovered ester.

Original languageEnglish
Pages (from-to)2105-2111
Number of pages7
JournalTetrahedron Asymmetry
Volume20
Issue number18
DOIs
Publication statusPublished - 2009 Sep 23

Fingerprint

octanes
enzymes
esters
Esters
Enzymes
acids
Acids
synthesis
Carbasugars
Oseltamivir
Enzyme kinetics
swine
Enantioselectivity
Esterases
Carboxylic Acids
Biological Products
Carboxylic acids
liver
carboxylic acids
Liver

ASJC Scopus subject areas

  • Organic Chemistry
  • Inorganic Chemistry
  • Physical and Theoretical Chemistry
  • Catalysis

Cite this

Enzyme-catalyzed resolution of 3,8-dioxatricyclo[3.2.1.02,4]octane-6-carboxylic esters and the application to the synthesis of 3-epishikimic acid. / Hamada, Manabu; Inami, Yoshikazu; Nagai, Yasuhito; Higashi, Toshinori; Shoji, Mitsuru; Ogawa, Seiichiro; Umezawa, Kazuo; Sugai, Takeshi.

In: Tetrahedron Asymmetry, Vol. 20, No. 18, 23.09.2009, p. 2105-2111.

Research output: Contribution to journalArticle

Hamada, Manabu ; Inami, Yoshikazu ; Nagai, Yasuhito ; Higashi, Toshinori ; Shoji, Mitsuru ; Ogawa, Seiichiro ; Umezawa, Kazuo ; Sugai, Takeshi. / Enzyme-catalyzed resolution of 3,8-dioxatricyclo[3.2.1.02,4]octane-6-carboxylic esters and the application to the synthesis of 3-epishikimic acid. In: Tetrahedron Asymmetry. 2009 ; Vol. 20, No. 18. pp. 2105-2111.
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