Enantiopure building blocks for chiral drugs from racemic mixtures of secondary alcohols by combination of lipase catalysis and Mitsunobu esterification.
The racemic alcohols 3-chloro-1-(2-thienyl)-1-propanol, 3-chloro-1-phenylpropanol, and 1-chloro-3-(3,4-difluorophenoxy)-2-propanol were converted into a mixture of one enantiomer as butanoate and the other as alcohol by lipase catalysis. Subsequent Mitsunobu esterification without separation proceeded with inversion of the unreacted alcohols to give high yield and ee of the three enantiopure butanoates. The butanoates of opposite configuration were produced in a similar manner, but starting with lipase-catalyzed hydrolysis of the racemic butanoates.
Liu
Hui-Ling
HL
Department of Chemistry, Norwegian University of Science and Technology, Trondheim, Norway.
Anthonsen
Thorleif
T
D000438:Alcohols / Q000737:chemistry* / Q000378:metabolism; D002087:Butyrates / Q000737:chemistry / Q000378:metabolism; D002384:Catalysis; D015195:Drug Design; D004951:Esterification; D066298:In Vitro Techniques; D008049:Lipase / Q000378:metabolism; D013237:Stereoisomerism
D000438:Alcohols; D002087:Butyrates; D008049:Lipase