Whole-cell yeast-mediated preparation of (R)-2-chloro-1-(3-nitrophenyl)ethanol as a synthetic precursor for (R)-phenylephrine

• P. minuta reduced 2-chloro-1-(3-nitrophenyl)ethanone to give (R)-alcohol.
• Substrate is easily prepared by nitration of 2-chlorophenylethanone.
• Amberlite XAD-7 effectively worked for a reservoir of the substrate.
• The product was transferred to (R)-phenylephrine, an α1-adrenergic receptor agonist.
• Five-step transformation proceeded without loss of the ee (98.0%).

The incubated whole-cell biocatalyst of Pichia minuta JCM 3622 reduced 2-chloro-1-(3-nitrophenyl)ethanone to provide (R)-2-chloro-1-(3-nitrophenyl)ethanol with 99.2% ee in 87% isolated yield in the presence of Amberlite XAD-7 as a reservoir for the hydrophobic, crystalline and toxic substrate. The product was transformed to (R)-1-(3-hydroxyphenyl)-2-methylaminoethanol (phenylephrine, 1a), a selective α1-adrenergic receptor agonist, in 98.0% ee over five steps.

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