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Preparation of enantiopure Wieland–Miescher ketone and derivatives by the MαNP acid method. Substituent effect on the HPLC separation
Author(s) -
Kasai Yusuke,
Shimanuki Kumiko,
Kuwahara Shunsuke,
Watanabe Masataka,
Harada Nobuyuki
Publication year - 2006
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.20236
Subject(s) - enantiopure drug , chemistry , diastereomer , substituent , ketone , solvolysis , organic chemistry , chromatography , high performance liquid chromatography , enantioselective synthesis , hydrolysis , catalysis
Enantiopure Wieland–Miescher ketone ( 4, W‐M ketone) and derivatives were prepared by the enantioresolution with 2‐methoxy‐2‐(1‐naphthyl)propionic acid (MαNP acid 1 ). Various racemic derivatives of 4 were esterified with acid ( S )‐(+)‐ 1 yielding diastereomeric MαNP esters, which were separated by HPLC on silica gel. It was clarified that the HPLC separation of diastereomers depended on the substituent of the derivatives, leading to the working hypothesis that MαNP acid esters of alcohols with less polar and more bulky aliphatic substituents are more effectively separated. The best separation was obtained in the case of tert ‐butyldimethylsilyl (TBDMS) ether derivative ( 12a / 12b ): separation factor α = 1.80, and resolution factor, Rs = 1.30. The 1 H NMR spectra of separated MαNP esters showed anomalously large magnetic anisotropy effects, from which their absolute configurations were determined. Solvolysis or reduction of the separated MαNP esters yielded alcohols, which were converted to enantiopure W‐M ketones 4. The results thus provided another route for preparation of enantiopure ketones (8a R )‐(−)‐ 4 and (8a S )‐(+)‐ 4. © 2006 Wiley‐Liss, Inc. Chirality