TY - JOUR
T1 - Examination of spacer effects on stereochemical recognition of a remote sterically hindered chiral center in lipase-catalyzed acylation
AU - Kobayashi, Ryohei
AU - Huang, Hanghang
AU - Hamada, Manabu
AU - Higashi, Toshinori
AU - Shoji, Mitsuru
AU - Sugai, Takeshi
N1 - Funding Information:
This work was supported both by a Grant-in-Aid for Scientific Research (No. 23580152 ) and formation of a research center in cell signaling drug discovery for molecular targeting therapies: matching fund subsidy 2009–2013 from the Ministry of Education, Culture, Sports, Science and Technology, Japan , and acknowledged with thanks. Amano Enzyme Inc., Novozymes Japan, and Meito Sangyo Co., Ltd. for the generous gift of lipases were acknowledged with thanks. H. H. thanks Professor Cai Jin, Faculty of Chemical and Biological Engineering, Zhejiang University, and office of student services (international) of Keio University, for “Independent Study I and II” of Keio international program (KIP) in 2009–2010, as an exchange student.
PY - 2012/9
Y1 - 2012/9
N2 - 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].
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].
KW - Acylation
KW - Hydrolysis
KW - Kinetic resolution
KW - Lipase
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U2 - 10.1016/j.molcatb.2012.05.006
DO - 10.1016/j.molcatb.2012.05.006
M3 - Article
AN - SCOPUS:84861828262
SN - 1381-1177
VL - 81
SP - 52
EP - 57
JO - Journal of Molecular Catalysis B: Enzymatic
JF - Journal of Molecular Catalysis B: Enzymatic
ER -