Highly enantioselective reduction of 3-chloro-2-oxoalkanoates with fermenting bakers' yeast. A new synthesis of optically active 3-chloro-2-hydroxyalkanoates and glycidic esters

Abstract

Reduction of 3-chloro-2-oxoalkanoic esters with fermenting bakers' yeast gave optically active 3-chloro-2-hydroxyalkanoic esters 2 (anti(2S,3R)/syn (2S,3S) = 52:48-90:10) in 50-85% yields with >95% ee except for 43% ee of ethyl syn-(2S,3S)-3-chloro-2-hydroxy-4-phenylbutanoate (2j). Compounds 2 were treated with NaOEt to give (E)-(2R,3S)-2,3-epoxyalkanoates 3 in 30-66% yields with 44-64%

Probing the mechanism of direct Mannich‐type α‐methylenation of ketoesters via electrospray ionization mass spectrometry

“…The starting esters 9 ,67–69 11 70 and 13 71 were prepared according to reported procedures. Ethyl benzoylacetate 1 (97% from Acros) and ethyl 2‐oxo‐4‐phenylbutyrate 3 (97% from Aldrich) were commercially available and used as provided.…”

Asymmetric Bioreduction of Ethyl 3-Halo-2-oxo-4-phenylbutanoate by Saccharomyces cerevisiae Immobilized in Ca-Alginate Beads with Double Gel Layer

“…1 H NMR coupling constants for 2-H and 3-H for syn-2a (δ 4.44, J 2,3 ) 1.8 Hz) and for anti-3a (δ 4.24, J 2,3 ) 2.6 Hz) have the same values as for syn-2b (δ 4.50, J 2,3 ) 1.8 Hz) and anti-3b (δ 4.46, J 2,3 ) 2.6 Hz), confirming the proposed absolute configuration for 2b ( 1 H NMR and 13 C NMR values matched those reported by Tsuboi). 34 In conclusion, we have developed a highly diastereo and enantioselective method for bioreduction of ethyl 3-halo-2oxo-4-phenylbutanoate to produce 3-halo-2-hydroxy-phenylbutanoates. Among the biocatalysts tested, S. cereVisiae gave the highest product yields, and the entrapment in alginate beads with double gel layers showed its efficacy in controlling the substrate concentration which is fundamental for the enantioselectivity and also for obtaining high syn: anti ratio of 3-halo-2-hydroxy-phenylbutanoates.…”

“…This method of cell entrapment was developed by Tanaka et al for continuous fermentation in the production of ethanol 31 and Chitinase. 32,33 Asymmetric reductions of 3-chloro-2-oxoalkanoates with fermenting baker's yeast have been reported by Tsuboi et al 34 The reduction of corresponding esters with baker's yeast gave optically active 3-chloro-2-hydroxyalkanoic esters (anti (2S,3R):syn (2S,3S) ) 52:48-90:10) in 50-85% yields and >95% ee, except for 43% ee of ethyl syn-(2S,3S)-3-chloro-2-hydroxy-phenylbutanoate. The reduction of 1a was achieved with good diastereoselectivity (anti (2S,3R)-3a:syn (2S,3S)-2a ) 66:34) and high enantioselectivity anti-(2S,3R)-3chloro-2-hydroxy-phenylbutanoate in 95% ee (Scheme 1).…”

“…The reduction of 1a was achieved with good diastereoselectivity (anti (2S,3R)-3a:syn (2S,3S)-2a ) 66:34) and high enantioselectivity anti-(2S,3R)-3chloro-2-hydroxy-phenylbutanoate in 95% ee (Scheme 1). The chiral 3-chloro-2-hydroxyalkanoic esters are very useful in the synthesis of chiral glycidic esters [34][35][36][37] and 2,3-epoxi alcohols, 38 which are key intermediates for the synthesis of important bioactive molecules. [34][35][36][37][38] In this work, we describe the asymmetric bioreduction of ethyl 3-halo-2-oxo-4-phenylbutanoate with several microorganisms, and especially with S. cereVisiae, which we have optimized by changing the matrix of immobilization and the concentration of substrate, and by feeding with glucose as electron donor.…”

“…The chiral 3-chloro-2-hydroxyalkanoic esters are very useful in the synthesis of chiral glycidic esters [34][35][36][37] and 2,3-epoxi alcohols, 38 which are key intermediates for the synthesis of important bioactive molecules. [34][35][36][37][38] In this work, we describe the asymmetric bioreduction of ethyl 3-halo-2-oxo-4-phenylbutanoate with several microorganisms, and especially with S. cereVisiae, which we have optimized by changing the matrix of immobilization and the concentration of substrate, and by feeding with glucose as electron donor. The entrapment of S. cereVisiae with double gel layers was fundamental to achieve high enantio-and diastereoselectivity.…”