Lipase-catalyzed transesterification of 2-hydroxy-2-(pentafluorophenyl)acetonitrile leading to (1R,2R)- and (1S,2S)-bis(pentafluorophenyl)ethane-1,2-diol

Optically pure (1R,2R)- and (1S,2S)-1,2-bis(pentafluorophenyl)ethane-1,2-diol (1) were synthesized from key intermediates (R)- and (S)-2-hydroxy-2-(pentafluorophenyl)acetonitrile (2), both of which were prepared by the lipase LIP-catalyzed transesterification (E = 465). The absolute configuration of (S)-2 was determined by X-ray structural analysis after transformation into (S)-alpha-cyano-2,3,4,5,6-pentafluorobenzyl (S)-6-methoxy-alpha-methyl-2-naphthaleneacetate (S,S)-9. In addition, the crystal structure of (S,S)-9 has an interesting well-ordered packing pattern which shows face-to-face stacking interactions and end-to-end parallel contacts between the pentafluorophenyl and 6-methoxynaphthyl groups of the adjacent molecules.

Differences in protein structure and similarities in catalytic function of two L-stereoselective carbonyl reductases from bakers' yeast.

We purified and studied two L-stereoselective carbonyl reductases from bakers' yeast (Saccharomyces cerevisiae). One catalyzed exclusively the enantioselective reduction of carbonyl compounds such as beta-keto esters and the other acted on alpha-acetoxy ketones and beta-keto esters. The enzymes had identical molecular weights and catalyzed the L-stereoselective reduction of various carbonyl compounds with similar substrate specificity, but they were different proteins coded by different genes.

Model for "charge-relay": acceleration by carboxylate anion in intramolecular general base-catalyzed ester hydrolysis by the imidazolyl group.

The effect of benzoate anion on intramolecular general base-catalyzed ester hydrolysis by the imidazolyl group in endo-5-[4'(5')-imidazolyl]bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate was examined in dioxane/H(2)O solutions. Benzoate anion exhibited a remarkable acceleration of the intramolecular general base-catalyzed hydrolysis of endo-5-[4'(5')-imidazolyl]bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate by the imidazolyl group. The rate of hydrolysis in the presence of the benzoate anion increased with the dioxane mole fraction and was proportional to the concentration of benzoate anion. On the other hand, the rate of hydrolysis of endo-5-[4'(5')-imidazolyl]bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate in the absence of benzoate anion decreased with the dioxane mole fraction. Thus, the ratio of the rate in the presence of benzoate anion to that in the absence of benzoate anion drastically increased with the dioxane mole fraction and attained a 2500-fold rate acceleration at a dioxane mole fraction of 0.42 (the highest experimentally attainable) when the concentration of benzoate anion was 0.5 M. The proposed mechanism involves proton abstraction by the benzoate anion from the imidazolyl group, followed by proton abstraction by the imidazolyl group from H(2)O, resulting in effective general base-catalysis of hydrolysis. The results of the present paper provide support for the "charge-relay" system in serine proteases.