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Chemoenzymatic Synthesis of Both Enantiomers of 2‐ tert ‐Butyl‐2‐methyl‐1,3‐benzodioxole‐4‐carboxylic (TBMB) Acid
Author(s) -
Higashi Toshinori,
Abe Chika,
Ninomiya Keiko,
Machida Takuya,
Chishima Nobuyuki,
Taketomi Shohei,
Furuta Miyu,
Komaki Yoko,
Senba Yoshihiko,
Tokuda Taeko,
Shoji Mitsuru,
Sugai Takeshi
Publication year - 2010
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201000446
Subject(s) - chemistry , acetal , diastereomer , enantiomer , alcohol , geotrichum , reactivity (psychology) , ketone , carboxylic acid , absolute configuration , stereoselectivity , medicinal chemistry , racemization , organic chemistry , lipase , stereochemistry , catalysis , enzyme , medicine , alternative medicine , food science , pathology
Both enantiomers of 2‐ tert ‐butyl‐2‐methyl‐1,3‐benzodioxole‐4‐carboxylic (TBMB) acid, which has a unique quaternary chiral center located on the acetal carbon, were prepared from a racemic ketone in which the carboxy group was replaced by a trifluoroacetyl group. First, reduction with fungi, Geotrichum candidum provided (2 S ,1′ S )‐ and (2 R ,1′ S )‐ 1′‐(2‐ tert ‐butyl‐2‐methyl‐1,3‐benzodioxol‐4‐yl)‐2′,2′,2′‐trifluoroethanol in a highly enantiofacially selective manner. After acetylation, the resulting diastereomeric mixture was submitted to Candida antarctica lipase B‐catalyzed transesterification. The reaction proceeded in a stereoselective manner under the influence of the chiral center at the acetal carbon, even though it was six atoms removed from the ester carbonyl carbon. Although the two substrates had the same absolute configuration at the secondary alcohol, the reaction rate of one stereoisomer was 72 times greater than that of the other isomer. The reason for this differential reactivity was attributed mainly to a large difference in V max(app) between the stereoisomers. The products, acetate and alcohol, were easily separated by chromatography, and each was then derivatized to ( R )‐ and ( S )‐TBMB acid, with >99.2% ee , respectively.