TY - JOUR
T1 - 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
AU - Hamada, Manabu
AU - Inami, Yoshikazu
AU - Nagai, Yasuhito
AU - Higashi, Toshinori
AU - Shoji, Mitsuru
AU - Ogawa, Seiichiro
AU - Umezawa, Kazuo
AU - Sugai, Takeshi
N1 - Funding Information:
The authors thank Professor Kaoru Nakamura of Institute for Chemical Research, Kyoto University, for his valuable discussion and encouragement on this study. Meito Sangyo Co. Ltd and Nagase ChemteX Co. were acknowledged with thanks, for generous gift of enzymes. This work was supported both by a Grant-in-Aid for Scientific Research (No. 18580106 ) and ‘High-Tech Research Center’ Project for Private Universities : matching fund subsidy 2006–2011 from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and acknowledged with thanks.
PY - 2009/9/23
Y1 - 2009/9/23
N2 - 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.
AB - 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.
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U2 - 10.1016/j.tetasy.2009.07.049
DO - 10.1016/j.tetasy.2009.07.049
M3 - Article
AN - SCOPUS:72049085783
SN - 0957-4166
VL - 20
SP - 2105
EP - 2111
JO - Tetrahedron Asymmetry
JF - Tetrahedron Asymmetry
IS - 18
ER -