Asymmetric reactions. XI. Sterical course of enzymatic reduction of methyl alkyl ketones and methyl aryl ketones

Baker's yeast mediated transformations in organic chemistry

“…Sterically hindered ketones (e.g., 4-octanone, tert-butyl methyl ketone, isobutyl isopropyl ketone, or n-amyl phenyl ketone) were not reduced at all. These results27, 28 the substrate is dissolved in a relatively non-toxic, water miscible solvent (e.g. ethanol, acetone, propylene glycol, DMSO, ethylene glycol monomethylether) prior to addition.…”

“…48 An analogous sequence of reduction and reoxidation for obtaining the pure enantiomers was used for preparation of enantiomerically pure methyl 5-chloro-2oxobicyclo[2.2.1]heptane-7-carboxylates (27) from the corresponding racemate (Scheme 9). Racemic 27 afforded upon treatment with BY 90% of a mixture of methyl (2S,5R,7S)-5-chloro-2-hydroxybicyclo[2.2.11heptane-7-carboxylate (28) and methyl (2S,5S,7R)-5chloro-2-hydroxybicyclo [2.2.1 ] heptane-7-carboxylate (29), which were each reoxidized by Cr03/H2S04/ acetone to yield both enantiomers of 27. A drawback of these reductions is the laborious workup, which could be improved by performing the reduction with Candida utilis and stopping the reduction at 52-53% conversion of racemic 27.49 Reduction of the racemic estradien derivative 37 (Scheme 11) with BY (Saccharomyces cerevisiae Heyen ex.…”

“…26 Fermentative reduction of substituted acetophenones 40a-j (Scheme 12) afforded (S)-l-arylethanols 41a-j in low to moderate yields and ee values between 82% and 96%. 27,28,50,[62][63][64][65][66][67][68] No influence on the steric course of the reduction was observed when the substituents were changed, but the velocity of the reaction was decreased by electron-donating substituents. 50,62 The advantage of yeast-mediated reductions of ketones is their high re selectivity, often resulting in high optical yields of products.…”

Product stereospecificity in the microbial reductions of hydroaromatic ketones

“…Both esters (4 and 5) were used to assign absolute stereochemistries because the quantities of each acid formed in the ozonolysis depend upon the structure of the starting acetate, i.e., one of the acids was not consistently the major ozonolysis product. In addition, 4 contained some dimethyl phthalate, which although optically inactive does affect the magnitude of the specific rotation.…”

Highly stereoselective reduction of haloketones using three new yeasts: application to the synthesis of (S)-adrenergic β-blockers related to propranolol

“…[1][2][3][4] The major advantage of using whole cells compared to the use of isolated reductases is the in vivo recycling of the red-ox co-enzymes (NADH or FADH 2 ). Saccharomyces cerevisiae (bakerÕs yeast), a readily available and cheap catalyst, has been the most extensively studied microorganism in this process.…”