73553-29-4

Upstream product

• 620-79-1 Ethyl 2-benzylacetoacetate 
• 56816-01-4 ethyl (S)-3-hydroxybutyrate 
• 100-39-0 benzyl bromide 
• 141-97-9 ethyl acetoacetate 

Downstream Products

• 92282-66-1 (3S,4S)-3-benzyl-4-methyl-2-oxetanone 
• 15324-90-0 (2Z)-but-2-en-1-ylbenzene 
• 935-00-2 trans-4-phenyl-2-butene 
• 107289-17-8 (2R,3R)-2-benzyl-3-hydroxy-butyric acid 
• 73553-31-8 (2S,3S)-2-benzyl-3-hydroxy-butyric acid 

Relevant academic research and scientific papers

Deracemization of diastereomerically pure syn- and anti-α-substituted β-hydroxyesters by Novozyme 435 lipase and determination of their absolute configuration by NMR spectroscopy

Enantiomerically pure α-substituted β-hydroxyesters are important chiral building blocks for ligands, auxiliaries and β-lactam antibiotics. A two-step chemo-enzymatic procedure using lipase as biocatalyst is an efficient way to synthesize such products. To date, the methods described are limited to molecules that do not contain a chiral center adjacent to the racemic carbinol, and furthermore, they are limited to acylation. Here, we investigated the deracemization of diastereomerically pure syn- and anti-α-substituted β-hydroxyesters containing two stereo centers, using experimental methods under neat conditions and classical molecule dynamics (MD) simulation. A screening of free and immobilized commercial lipases identified immobilized lipase B from Candida antarctica (Novozyme 435) as the most appropriate biocatalyst for sterically demanding α-substituted β-hydroxyesters. Using Novozyme 435, reaction conditions were optimized and hydroxyesters (3S) or (3R) were achieved with enantiomeric excesses up to ≥99% ee and maximum overall yields of 80%. The absolute configuration of the enantiomers was eventually determined by 1H-NMR spectroscopy after derivatization with MOSHER'S reagent (α-methoxy-α-trifluoromethylphenylacetic acid = MTPA).

Enantioselective and Diastereoselective Ir-Catalyzed Hydrogenation of α-Substituted β-Ketoesters via Dynamic Kinetic Resolution

An iridium/f-amphol catalytic system for the enantioselective hydrogenation of α-substituted β-ketoesters via dynamic kinetic resolution is reported. The desired anti products were obtained in high yields (up to 98%) with good diastereoselectivity (up to 96:4 diastereometic ratio (dr)) and excellent enantioselectivity (up to >99% enantiomeric excess (ee)). A catalytic model is proposed to explain the stereoselectivity.

Klebsiella pneumoniae (NBRC 3319) mediated asymmetric reduction of α-substituted β-oxo esters and its application to the enantioiselective synthesis of small-ring carbocycle derivatives

Ketoreductases from Klebsiella pneumoniae (NBRC 3319) selectively reduce several 2-substituted ethyl 3-oxobutyrates to yield the corresponding syn-β-hydroxy esters with remarkable stereocontrol (de > 99%, ee > 99%). The enantiopure hydroxy oxo esters were

A recombinant ketoreductase tool-box. Assessing the substrate selectivity and stereoselectivity toward the reduction of β-ketoesters

The substrate selectivity and stereoselectivity of a series of ketoreductases were evaluated toward the reduction of two sets of β-ketoesters. Both the structural variety at β-position and the substituent at α-position greatly affected the activity and stereoselectivity of these ketoreductases. For the first set of β-ketoesters, at least one ketoreductase was found that catalyzed the formation of either (d) or (l) enantiomer of β-hydroxyesters from each substrate with high optical purity, with the only exception of ethyl (d)-3-hydroxy-3-phenylpropionate. For the second set of β-ketoesters with α-substituents, the situation is more complex. More commonly, a ketoreductase was found that formed one of the four diastereomers in optically pure form, with only a few cases in which enzymes could be found that formed two or more of the diastereomers in high optical purity. The continued development of new, more diverse ketoreductases will create the capability to produce a wider range of single diastereomers of 2-substituted-3-hydroxy acids and their derivatives.

THE STEREOSELECTIVE α-ALKYLATION OF CHIRAL β-HYDROXY ESTERS AND SOME APPLICATIONS THEREOF

The stereoselectivity of the α-alkylation of chiral β-hydroxy ester is discussed.The configuration of the alkylated product was proved chemically (Scheme 2) .A one pot aldol-alkylation reaction was developed leading stereoselectively to racemic(S*,S*)-α-alkyl-β-hydroxy ester (Scheme 3,4) .Baker's yeast reduction of 2-alkyl-3-keto ester led to valuable chiral (2RS,3S)-intermediates, which were converted via the corresponding dianion to compounds with a chiral quaternary C atom (Scheme 6) .Synthetic applications of the above findings are shown in the synthesis of various chiral compounds (Scheme 8 and 9) .