[Lipase-catalyzed kinetic resolution of 2-substituted cycloalkanols].
Racemates of cis- and trans-2-cyanocyclopentanol and -cyclohexanol, cis- and trans-2-dialkylaminomethylcyclopentanol, -cyclohexanol and -cycloheptanol and Boc-protected cis- and trans-2-methylhydrazinocyclopentanol and -cyclohexanol were resolved through lipase PS (from Pseudomonas cepacia) or Novozym 435 (from Candida antarctica B)-catalysed asymmetric acylation. High enantioselectivity (E > 200) was observed when vinyl acetate was used as acylating agent, with diethyl ether or with diisopropyl ether as solvent. Reaction rates were markedly affected by the solvent and by the quantity of the enzyme. The size of the cycloalkane ring had a clear effect on the rate of enantioselective acylation: the acetylations of the five-membered cycloalcanols proceeded more rapidly than those of the six-membered ones and much more rapidly than those of the seven-membered systems. It can also be concluded that the trans isomers react more rapidly than the cis counterparts, the only exception being found in the case of 2-cyanocyclohexanols. In good correlation with the "Kazlauskas rule", in all cases, the (R) enantiomer is acylated faster than the (S) enantiomer, yielding an (R) ester and an (S) alcohol, which products from large-scale experiments were separated by column chromatography. During these studies, a total of 18 racemates of cis- and trans-2-substituted cycloalkanols were resolved by using lipases as catalysts, and 52 enantiomers (50 of them new) were characterized by NMR, elemental analysis and ocasionally MS.
Forró
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Szegedi Tudományegyetem, Gyógyszerkémiai Intézet, 6701 Szeged, POB 121.
D000107:Acetylation; D000215:Acylation; D000438:Alcohols / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D004800:Enzymes, Immobilized / Q000378:metabolism; D004952:Esters / Q000378:metabolism; D005656:Fungal Proteins; D006844:Hydrocarbons, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008049:Lipase / Q000378:metabolism*; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000438:Alcohols; D004800:Enzymes, Immobilized; D004952:Esters; D005656:Fungal Proteins; D006844:Hydrocarbons, Cyclic; C093667:Novozyme 435; D008049:Lipase
2-szubsztituált cikloalkanolok lipáz-katalizálta kinetikus rezolválása.