Lipase-catalyzed kinetic resolution of a series of esters having a sulfoxide group as the stereogenic centre

Allenmark, Stig; Andersson, Arne

doi:10.1016/s0957-4166(00)80104-4

Cited by 18 publications

(3 citation statements)

References 13 publications

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“…The degree of enantioselectivity was lower than previous resolutions (20,21) where the sulfoxide was in the acid portion of the ester. Thus, putting the sulfoxide in the alcohol portion does not seem to be a good general strategy for resolution of sulfoxides.…”

Section: Discussionmentioning

confidence: 39%

Kinetic resolution of sulfoxides with pendant acetoxy groups using cholesterol esterase: substrate mapping and an empirical rule for chiral phenols

Serreqi¹,

Kazlauskas²

1995

Can. J. Chem.

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Sulfoxides are valuable chiral auxiliaries because they direct the formation of carbon~arbon bonds. As a route to enantiomerically pure sulfoxides, we examined hydrolase-catalyzed kinetic resolution by hydrolysis of apendant acetoxy group. Screening hydrolases for the enantioselective hydrolysis of the acetate in 2-(methylsulfiny1)phenyl acetate, lb, identified cholesterol esterase (CE) as the most enantioselective enzyme. The enantiomeric ratio, E, ranged from 10 to 25, favoring the (R) configuration at sulfur. Competing chemical hydrolysis of l b caused the large range in the measured values of E. A small-scale (250 mg) resolution of (2)-l b yielded (S)-lb with >99% ee (1 1 % yield) after recrystallization. Changing the methyl substituent to phenyl or n-butyl did not significantly change the enantioselectivity (E = 10 and 15, respectively), but changing it to a chloromethyl substituent lowered the enantioselectivity slightly (E = 5). Changing the phenyl acetate to a naphthyl acetate (2-(phenylsulfiny1)phenyl acetate vs. 1-(phenylsulfiny1)-2-naphthyl acetate) increased the enantioselectivity from 10 to 19. In all cases CE favored the (R)-sulfoxide. To aid the design of new resolutions with CE, we propose an empirical rule that accounts for the observed enantiopreference of CE toward these 5 sulfoxides and 15 other chiral aryl acetates. This empirical rule uses both the size of the substituents and their conformational preferences to predict which enantiomer reacts faster.Key words: kinetic resolution, lipase, cholesterol esterase, sulfoxides, empirical rule, Resume : Les sulfoxydes sont des auxiliaires chiraux utiles parce qu'ils orientent la formation de liaisons carbone-carbone. Dans le but d'obtenir des sulfoxydes Cnantiomeriquement purs, on a examine la possibilitC d'utiliser une rtsolution cinCtique catalysCe par une hydrolase impliquant l'hydrolyse d'un groupe acCtoxy. Une Cvaluation des hydrolases pour leur capacitt a effectuer l'hydrolyse CnantiosClective de llacCtate de 2-(mCthylsulfinyl)phCnyle, lb, a permis d'identifier 13estCrase de cholestCro1 (CE) comme l'enzyme le plus CnantiosClectif. Le rapport CnantiomCrique, E, vane de 10 a 25 et il favorise la configuration (R) au niveau du soufre. L'hydrolyse chimique compCtitive du composC l b provoque les grandes variations observkes dans les valeurs mesurCes de E. Une rCsolution preparative 5 faible Cchelle (250 mg) du composC (2)-lb conduit, aprks recristallisation, au (S)-lb avec un ee >99% (rendement de 11%). Lorsqu'on change le substituant de mCthyle 2 phCnyle ou n-butylC, il n'y a pas de changement significatif d'CnantiosClectivitC (E = 10 et 15, respectivement); toutefois, si on le remplace par un chloromCthyle, 1'CnantiosClectivitC est 1Cgkrement diminuCe (E = 5). Si l'on remplace I'acttate de phCnyle par 1'acCtate de naphtyle (acCtate de 2-(phCnylsulfiny1)phtnyle vs. acetate de 1-(phCnylsulfiny1)-2-naphtyle) 1'CnantiosClectivitC passe de 10 a 19. Dans tous les cas, la CE favorise le (R)-sulfoxyde. Dans le but d'aider au dtveloppement de...

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Section: Discussionmentioning

confidence: 39%

Kinetic resolution of sulfoxides with pendant acetoxy groups using cholesterol esterase: substrate mapping and an empirical rule for chiral phenols

Serreqi¹,

Kazlauskas²

1995

Can. J. Chem.

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“…The compounds studied in this paper have been synthesized in our laboratory according to methods described earlier, 1a-d and 2d, 8 2a-b, 10 and 2c. 11 The methyl esters 2e-f were prepared by addition of diazomethane (generated from N-nitroso-N-methyl-p-toluene-sulfonamide [Fluka, Buchs, Switzerland] and distilled) to a solution of the sulfoxide 2c in methanol, followed by evaporation of the solvent.…”

Section: Materials and Methods Chemicalsmentioning

confidence: 99%

“…The tailing effect is more pronounced on CSP I than on CSP II, and Figure 3 shows how a substantial improvement of efficiency and resolution of the enantiomers of 2a is obtained by adding a small amount of formic acid (0.05%, v/v) to the mobile phase. The elution order, (+)-(R) prior to (−)-(S), of the enantiomers of 2a-b on CSP I, has been determined previously, 10 and also holds for CSP II. The overall gain of adding an acidic additive is primarily an improvement of peak shape, but also a slight decrease in retention for all the analytes, with essentially unchanged selectivity.…”

Section: Significance Of Hydrogen Bondingmentioning

confidence: 99%