Chan Seong Cheong

Chemoenzymatic Synthesis of Optically Active 2-Phenyl-2-(1H-1,2,4-triazol-1-ylmethyl)hexanenitrile

Abstract (±)-2-Cyano-2-phenyl-1-hexanol 3 was resolved to each enantiomer using Candida rugosa and Pseudomonas fluorescens lipases in 62 and 99% ee, respectively. The absolute stereochemistry of one of the enantiomers was determined to be (S) by diastereomeric amide formation and X-ray crystallography. The resolved alcohols of (R)- and (S)-isomer were transformed to Systhane® analogues.

Enzyme-catalysed improved resolution of (RS)-4-cyano-4-(3,4-dimethoxyphenyl)-4-isopropyl-1-butanol

Abstract Resolutions of ( RS )-4-cyano-4-(3,4-dimethoxyphenyl)-4-isopropyl-1-butanol 1 using various enzymes were performed. Among them, Pseudomonas fluorescens resolved it with moderate stereoselectivity ( E =13) and reacted faster with the ( S )-enantiomer. To optimize enzyme-catalysed reaction conditions for the resolution, the effect of solvents and additives was studied. In n -hexane:ethyl acetate (9:1), both reaction rate and selectivity were high. When pyridine, potassium carbonate and molecular sieves were used as additives, the enantiomeric excess of the ( R )-enantiomer was 99, 99 and 98% at 52–60% conversion, respectively. However, in diisopropyl ether, the enantiomeric excess of unreacted alcohol ( R )- 1 was up to 99% at 70% conversion without additives.

Enzymatic kinetic resolution of ketorolac

Abstract Ketorolac 1 was resolved into each enantiomer by interesterification using lipase B from Candida antarctica . The acid reacted with various alcohols and the ester and acid were resolved up to >99% e.e. when reacted with octanol, which was the best result. To increase reactivity and enantioselectivity, the experimental conditions were adjusted by varying temperature, solvent, alcohols and reaction time.

Lipase-catalyzed resolution of 1,3-dioxolane derivatives: synthesis of a homochiral intermediate for antifungal agents

Abstract Dioxolane alcohol (±)- 1 and the corresponding acid (±)- 2 were kinetically resolved into their respective enantiomers by lipase-catalyzed hydrolysis and esterification reactions. Various alcohols were tested to resolve the acid (±)- 2 , and the desired (2 R ,4 R )-isomer of the acid was obtained with >96% ee as the best result. Halogenated solvents such as methylene chloride and 1,2-dichloroethane were found to raise the reactivity and selectivity of the system. After recrystallization, the purity of the desired (2 R ,4 R )-acid could be increased to over 98% ee.