Novel chemoenzymatic strategy for the synthesis of enantiomerically pure secondary alcohols with sterically similar substituents.
A novel chemoenzymatic strategy for the synthesis of enantiomerically pure secondary alcohols with sterically similar substituents is described. The key step is the kinetic lipase-catalyzed resolution of racemic mixtures of substituted propargylic alcohols. The efficiency of this new approach was tested in the preparation of the corresponding enantiomers of 1,11-hexadecandiol derivatives ((R)-5 and (S)-5). Two strategies were tested. In the first one, the racemic intermediate 1-octyn-3-ol (1) was resolved enzymatically and then elongated with 1-bromo-9,11-dioxadodecane. Alternatively, the racemic 1 can be elongated to the corresponding racemic 17,19-dioxa-7-eicosyn-6-ol (3) first and then resolved biocatalytically. Twelve commercially available lipases were screened for the kinetic resolution of these intermediates. Among them, Candida antarctica lipase (CAL-B) and Humicola lanuginosa lipase (HLL) were the best biocatalysts for the resolution of 1 (S enantiomer 90% ee, E = 35), and 3 (R enantiomer 90% ee, E = 34), respectively.
Abad
José-Luis
JL
Department of Biological Organic Chemistry, IIQAB-CSIC, Jordi Girona 18-26, 08034-Barcelona, Spain.
Soldevila
Carles
C
Camps
Francisco
F
Clapés
Pere
P
D000215:Acylation; D000438:Alcohols / Q000138:chemical synthesis*; D002175:Candida / Q000201:enzymology*; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D005658:Fungi / Q000201:enzymology*; D006865:Hydrogenation; D007700:Kinetics; D008049:Lipase / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013237:Stereoisomerism
D000438:Alcohols; D008049:Lipase