AI Article Synopsis
- Enantiopure β-nitroalcohols are vital for synthesizing pharmaceutical compounds, particularly β-adrenergic blockers.
- The study showcases the engineered enzyme HHDHamb, which allows for the selective bio-nitration of phenyl glycidyl ethers to produce chiral β-nitroalcohols using safe nitrite nitrating agents.
- The method achieved high yields and optical purity, and successfully synthesized two enantiomers of the β-adrenergic blocker metoprolol using these β-nitroalcohols as starting materials.
Article Abstract
Enantiopure β-nitroalcohols, as an important class of nitro-containing compounds, are essential building blocks in pharmaceutical and organic chemistry, particularly for the synthesis of β-adrenergic blockers. In this study, we present the successful protein engineering of halohydrin dehalogenase HHDHamb for the enantioselective bio-nitration of various phenyl glycidyl ethers to the corresponding chiral β-nitroalcohols, using the inexpensive, commercially available, and safer nitrite as a nitrating agent. The chiral (R)- and (S)-1-nitro-3-phenoxypropan-2-ols were synthesized by the several enantiocomplementary HHDHamb variants through the whole-cell biotransformation, which showed good catalytic efficiency (up to 43% isolated yields) and high optical purity (up to >99% ee). In addition, we also demonstrated that the bio-nitration method was able to tolerate the substrate at a high concentration of 1000 mM (150 g/L). Furthermore, representative synthesis of two optically active enantiomers of the β-adrenergic blocker metoprolol was successfully achieved by utilizing the corresponding chiral β-nitroalcohols as precursors.
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| http://dx.doi.org/10.1016/j.bioorg.2023.106640 | DOI Listing |
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