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Applying Lipase Catalysis to Access the Enantiomers of Dorzolamide Intermediates
Author(s) -
Turcu Mihaela C.,
Rantapaju Maria,
Kanerva Liisa T.
Publication year - 2009
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200900672
Subject(s) - chemistry , kinetic resolution , enantiomer , lipase , epimer , substrate (aquarium) , acylation , catalysis , stereochemistry , organic chemistry , enantiomeric excess , enantioselective synthesis , enzyme , oceanography , geology
The kinetic resolution of three dorzolamide intermediates has been studied in the presence of Burkholderia cepacia lipase in organic solvents. All the stereoisomers of 6‐methyl‐5,6‐dihydro‐4 H ‐thieno[2,3‐ b ]thiopyran‐4‐ol were prepared starting from the racemic cis ‐dihydrothiopyranol intermediate giving first the 4 R ,6 S and 4 S ,6 R enantiomers. Subsequent epimerization and purification of the trans enantiomers by enzymatic acylation or alcoholysis then gave the cis enantiomers. The cis ‐4‐hydroxy‐6‐methyl‐5,6‐dihydro‐4 H ‐thieno[2,3‐ b ]thiopyran 7,7‐dioxide enantiomers were also prepared by enzymatic kinetic resolution. The kinetic resolution of ethyl 3‐(2‐thienylthio)butanoate with lipases gave moderate enantioselectivities but the method was not used on a preparative scale with this substrate. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)