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Synthesis 2010(17): 2931-2934  
DOI: 10.1055/s-0030-1258167
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Enantioselective Total Synthesis of (R)-α-Lipoic Acid: An Application of Thermodynamically Controlled Deracemization of (±)-2-(2-Methoxyethyl)cyclohexanone

Hiroto Kaku*, Natsuko Okamoto, Takeshi Nishii, Mitsuyo Horikawa, Tetsuto Tsunoda*
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770-8514, Japan
Fax: +81(88)6553051; e-Mail: kaku@ph.bunri-u.ac.jp; e-Mail: tsunoda@ph.bunri-u.ac.jp;
Further Information

Publication History

Received 18 March 2010
Publication Date:
12 July 2010 (online)

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Abstract

According to the concept of thermodynamically controlled deracemization, racemic 2-(2-methoxyethyl)cyclohexanone was converted into the R-isomer (99% ee) in 90% yield using (-)-(2R,3R)-trans-2,3-bis(hydroxydiphenylmethyl)-1,4-dioxaspi­ro[5.4]decane as a host molecule under basic conditions. As an application, a short and enantioselective synthesis of (R)-α-lipoic acid was accomplished in 44% overall yield from (±)-2-(2-methoxyethyl)cyclohexanone.

Key words

(R)-α-lipoic acid - deracemization - molecular recognition - host-guest systems - asymmetric synthesis

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