Enantiocomplementary synthesis of ß-adrenergic blocker precursors via biocatalytic nitration of phenyl glycidyl ethers.
Bioorg Chem
; 138: 106640, 2023 09.
Article
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| MEDLINE
| ID: mdl-37320911
ABSTRACT
Enantiopure ß-nitroalcohols, as an important class of nitro-containing compounds, are essential building blocks in pharmaceutical and organic chemistry, particularly for the synthesis of ß-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 ß-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 ß-adrenergic blocker metoprolol was successfully achieved by utilizing the corresponding chiral ß-nitroalcohols as precursors.
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1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Éteres Fenílicos
/
Antagonistas Adrenérgicos beta
Idioma:
En
Revista:
Bioorg Chem
Año:
2023
Tipo del documento:
Article