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

ASJC Scopus subject areas

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

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