Synthesis of the antistroke drug lubeluzole and its enantiomer. Lipase-catalyzed resolution of chiral building block.
1-Chloro-3-(3,4-difluorophenoxy)-2-propanol was kinetically resolved by lipase-catalyzed esterification with vinyl butanoate in organic medium to yield the (S)-butanoate and the (R)-alcohol as the remaining substrate. In an enantioconvergent synthesis the mixture was subject to Mitsunobu esterification in one pot which converted the (R)-alcohol to the (S)-ester. The (S)-butanoate was hydrolyzed by lipase catalysis to give (S)-1-chloro-3-(3,4-difluorophenoxy)-2-propanol. The two enantiopure chiral building blocks were used for synthesis of Lubeluzole and its enantiomer respectively.
Liu
H L
HL
Department of Chemistry, Norwegian University of Science and Technology, N-7491 Trondheim, Norway.
Hoff
B H
BH
Berg
T C
TC
Anthonsen
T
T
D002317:Cardiovascular Agents / Q000138:chemical synthesis*; D002384:Catalysis; D008049:Lipase / Q000737:chemistry*; D010880:Piperidines / Q000138:chemical synthesis*; D020005:Propanols / Q000737:chemistry / Q000302:isolation & purification; D013237:Stereoisomerism; D013379:Substrate Specificity; D013844:Thiazoles / Q000138:chemical synthesis*
D002317:Cardiovascular Agents; D010880:Piperidines; D020005:Propanols; D013844:Thiazoles; D008049:Lipase; C097722:lubeluzole