Ethyl (R)-(+)-4-chloro-3-hydroxybutyrate

• CAS: 90866-33-4
• Catalog Number: ACM90866334
• Category: Main Products
• Molecular Weight: 166.60
• Molecular Formula: ClCH2CH(OH)CH2CO2C2H5
• Synonyms: ethyl (3R)-4-chloro-3-hydroxybutanoate
• IUPAC Name: ethyl(3R)-4-chloro-3-hydroxybutanoate
• SMILES: CCOC(=O)CC(CCl)O
• InChI Key: ZAJNMXDBJKCCAT-RXMQYKEDSA-N
• Boiling Point: 93-95ºC (5 mmHg)
• Melting Point: 93-95ºC
• Flash Point: 109ºC
• Density: 1.19
• Appearance: colorless to light yellow transparent liquid
• Exact Mass: 166.04000
• Hazard Statements: Xi:Irritant
• Packing Group: III
• Safety Description: S26-S36

Case Study

Efficient Biocatalytic Production of Ethyl (R)-4-chloro-3-hydroxybutyrate Using a Novel Carbonyl Reductase

Chen, Xiang, et al. BMC biotechnology 16.1 (2016): 70.

Ethyl (R)-4-chloro-3-hydroxybutyrate ((R)-CHBE) is a high-value chiral synthon required for the manufacture of several pharmaceuticals, such as L-carnitine and some neuromodulators. The enzymatic asymmetric synthesis is the preferred mode of production, however the previously reported biocatalytic routes for (R)-CHBE have significant limitations, presenting a demand to develop an improved, more robust process.
A novel stereoselective carbonyl reductase (BgADH3) was discovered and utilized for the reduction of prochiral ethyl 4-chloro-3-oxobutanoate (COBE) to (R)-CHBE. BgADH3, which was isolated from Burkholderia gladioli, was shown to have high activity and enantioselectivity for this transformation.
Key Results
· To create an efficient production system, the BgADH3 enzyme was implemented in a whole-cell biocatalyst. Recombinant E. coli cells were engineered to co-express both BgADH3 and a glucose dehydrogenase, creating an integrated system for cofactor (NADPH) regeneration. This design eliminated the need for adding expensive external cofactors.
· The bioconversion was successfully scaled using a substrate fed-batch strategy in an aqueous/octanol biphasic system, which helped manage substrate and product inhibition. This optimized process achieved the complete conversion of 1200 mmol of COBE, producing (R)-CHBE with excellent enantiomeric excess (>99.9%). The process demonstrated high productivity, with a space-time yield of 4.47 mmol/L/h·g DCW^-1.