Examination of spacer effects on stereochemical recognition of a remote sterically hindered chiral center in lipase-catalyzed acylation

Ryohei Kobayashi, Hanghang Huang, Manabu Hamada, Toshinori Higashi, Mitsuru Shoji, Takeshi Sugai

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

To date, the enzyme-catalyzed kinetic resolution of the secondary alcohol [Ar-C*H(CH 3)OH, Ar = 2′,4′,6′- triisopropylphenyl] has not been available, due to high steric hindrance around the hydroxy group. To achieve resolution, the reaction site was extended by the introduction of two kinds of spacers, [-C(=O)CH 2] and [-C(=O)C**HCN]. In the first substrate, the recognition of remote chirality [Ar-C*H(CH 3)O-C(=O)CH 2OH] by acylation with Burkholderia cepacia lipase was examined by changing reaction conditions and acyl donors. An E = 22 in the preference of (1′R)-isomer, was recorded with vinyl acetate as an acyl donor at 25 °C. In the second substrate, there was a matched enantiomeric pair [stereoselective ratio at C-1′ = 15, in the preference of (1′R)-isomer] and a mismatched pair [stereoselective ratio at C-1′ = 2.5, in the preference of (1′S)-isomer] based on the relative stereochemistry between the two chiral centers [Ar- C*H(CH 3)O-C(=O)C**HCN-OH].

Original languageEnglish
Pages (from-to)52-57
Number of pages6
JournalJournal of Molecular Catalysis B: Enzymatic
Volume81
DOIs
Publication statusPublished - 2012 Sep

Fingerprint

Burkholderia cepacia
Acylation
Lipases
Lipase
Isomers
Alcohols
Enzymes
Enzyme kinetics
Stereochemistry
Chirality
Substrates
vinyl acetate

Keywords

  • Acylation
  • Hydrolysis
  • Kinetic resolution
  • Lipase

ASJC Scopus subject areas

  • Biochemistry
  • Bioengineering
  • Catalysis
  • Process Chemistry and Technology

Cite this

Examination of spacer effects on stereochemical recognition of a remote sterically hindered chiral center in lipase-catalyzed acylation. / Kobayashi, Ryohei; Huang, Hanghang; Hamada, Manabu; Higashi, Toshinori; Shoji, Mitsuru; Sugai, Takeshi.

In: Journal of Molecular Catalysis B: Enzymatic, Vol. 81, 09.2012, p. 52-57.

Research output: Contribution to journalArticle

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AU - Shoji, Mitsuru

AU - Sugai, Takeshi

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AB - To date, the enzyme-catalyzed kinetic resolution of the secondary alcohol [Ar-C*H(CH 3)OH, Ar = 2′,4′,6′- triisopropylphenyl] has not been available, due to high steric hindrance around the hydroxy group. To achieve resolution, the reaction site was extended by the introduction of two kinds of spacers, [-C(=O)CH 2] and [-C(=O)C**HCN]. In the first substrate, the recognition of remote chirality [Ar-C*H(CH 3)O-C(=O)CH 2OH] by acylation with Burkholderia cepacia lipase was examined by changing reaction conditions and acyl donors. An E = 22 in the preference of (1′R)-isomer, was recorded with vinyl acetate as an acyl donor at 25 °C. In the second substrate, there was a matched enantiomeric pair [stereoselective ratio at C-1′ = 15, in the preference of (1′R)-isomer] and a mismatched pair [stereoselective ratio at C-1′ = 2.5, in the preference of (1′S)-isomer] based on the relative stereochemistry between the two chiral centers [Ar- C*H(CH 3)O-C(=O)C**HCN-OH].

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