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Asymmetric synthesis and stereochemical structure–activity relationship of (R)- and (S)-8-[1-(2,4-dichlorophenyl)-2-imidazol-1-yl-ethoxy] octanoic acid heptyl ester, a potent inhibitor of allene oxide synthase by Keimei Oh; Yoichiro Shimura; Kyoko Ishikawa; Yudai Ito; Tadao Asami; Noboru Murofushi; Yuko Yoshizawa is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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The preparation of both enantiomers of 8-[1-(2,4-dichlorophenyl)-2-imidazol-1-yl-ethoxy] octanoic acid heptyl ester (JM-8686), a potent inhibitor of allene oxide synthase, has been achieved using 2,4-dichlorophenacyl bromide as a starting material. The key step was the asymmetric reduction of 1-(2,4-dichlorophenyl)-2-imidazol-1-yl-ethanone with chiral BINAL-H. The products were purified by chiral high-performance liquid chromatography (HPLC) to afford pure (R)-JM-8686 and (S)-JM-8686. The inhibitory activities and binding affinities of these enantiomers toward allene oxide synthase were determined. We found that the inhibition potency of (R)-JM-8686 is approximately 200 times greater than that of (S)-JM-8686, with IC 50 values of approximately 5 ± 0.2 nM and 950 ± 18 nM, respectively. The dissociation constants of (R)-JM-8686 and (S)-JM-8686 with respect to the recombinant allene oxide synthase were approximately 1.4 ± 0.3 lM and 4.8 ± 0.6 lM, respectively.

Who reads Asymmetric synthesis and stereochemical structure–activity relationship of (R)- and (S)-8-[1-(2,4-dichlorophenyl)-2-imidazol-1-yl-ethoxy] octanoic acid heptyl ester, a potent inhibitor of allene oxide synthase?

Author

Keimei Oh; Yoichiro Shimura; Kyoko Ishikawa; Yudai Ito; Tadao Asami; Noboru Murofushi; Yuko Yoshizawa

Publisher

Elsevier Science; Elsevier ; Elsevier Ltd.; Elsevier BV (ISSN 0968-0896)

Published

2008

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)