Resolution of racemic cis-1-amino-2-indanol by diastereomeric salt formation with (S)-2-phenylpropionic acid

“…Cycloalkanediamine derivatives as activated factor X (fXa) for the therapy of thrombosis and related diseases [3] . Indinavir, an important biologically active compound as a human immunodeficiency virus (HIV) protease inhibitor [4] . In addition, Ethambutol (EMB), an important anti‐tubercular drug, [5] can be prepared directly from ( S )‐(+)‐2‐aminobutan‐1‐ol.…”

Section: Methodsmentioning

confidence: 99%

“…[3] Indinavir, an important biologically active compound as a human immunodeficiency virus (HIV) protease inhibitor. [4] In addition, Ethambutol (EMB), an important anti-tubercular drug, [5] can be prepared directly from (S)-(+)-2-aminobutan-1-ol. The importance of chiral β-amino alcohols has attracted continuous and significant attention from the synthetic groups, and a variety of chemical strategies have been developed for the synthesis of these chiral chemicals.…”

mentioning

confidence: 99%

Enantioselective Cascade Biocatalysis for Deracemization of Racemic β‐Amino Alcohols to Enantiopure (S)‐β‐Amino Alcohols by Employing Cyclohexylamine Oxidase and ω‐Transaminase

et al. 2020

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Optically active β-amino alcohols are very useful chiral intermediates frequently used in the preparation of pharmaceutically active substances. Here, a novel cyclohexylamine oxidase (ArCHAO) was identified from the genome sequence of Arthrobacter sp. TYUT010-15 with the R-stereoselective deamination activity of β-amino alcohol. ArCHAO was cloned and successfully expressed in E. coli BL21, purified and characterized. Substrate-specific analysis revealed that ArCHAO has high activity (4.15 to 6.34 U mg À 1 protein) and excellent enantioselectivity toward the tested β-amino alcohols. By using purified ArCHAO, a wide range of racemic β-amino alcohols were resolved, (S)-β-amino alcohols were obtained in > 99 % ee. Deracemization of racemic β-amino alcohols was conducted by ArCHAO-catalyzed enantioselective deamination and transaminase-catalyzed enantioselective amination to afford (S)-β-amino alcohols in excellent conversion (78-94 %) and enantiomeric excess (> 99 %). Preparative-scale deracemization was carried out with 50 mM (6.859 g L À 1) racemic 2-amino-2-phenylethanol, (S)-2-amino-2-phenylethanol was obtained in 75 % isolated yield and > 99 % ee.

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“…Enantiopure β-amino alcohols are important high value chemicals used in the preparation of pharmaceutics [1] such as randolazine, [2] nebivolol and metoprolol, [3] as a ligand for chiral catalysts in asymmetric synthesis, and as a chiral building block in the synthesis of other chiral compounds. Specifically, (R)-2-phenylglycinol 1 a is used in the synthesis of novel antibiotic pyrazolopyrimidines, EGFR inhibitor thienopyrimidines, and 3-phosphoinositide-dependent protein kinase-1 (PDK1) inhibitor.…”

Section: Introductionmentioning

confidence: 99%

Bioproduction of Enantiopure (R)‐ and (S)‐2‐Phenylglycinols from Styrenes and Renewable Feedstocks

et al. 2020

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Enantiopure (R)-and (S)-2-phenylglycinols are important chiral building blocks for pharmaceutical manufacturing. Several chemical and enzymatic methods for their synthesis were reported, either involving multi-step synthesis or starting from a relatively complex chemical. Here, we developed one-pot simple syntheses of enantiopure (R)-and (S)-2-phenylglycinols from cheap starting materials and renewable feedstocks. Enzyme cascades consisting of epoxidation-hydrolysis-oxidation-transamination were developed to convert styrene 2 a to (R)-and (S)-2-phenylglycinol 1 a, with butanediol dehydrogenase for alcohol oxidation as well as BmTA and NfTA for (R)-and (S)-enantioselective transamination, respectively. The engineered E. coli strains expressing the cascades produced 1015 mg/L (R)-1 a in > 99% ee and 315 mg/L (S)-1 a in 91% ee, respectively, from styrene 2 a. The same cascade also converted substituted styrenes 2 b-k and indene 2 l into substituted (R)-phenylglycinols 1 b-k and (1R, 2R)-1-amino-2-indanol 1 l in 95-> 99% ee. To transform biobased L-phenylalanine 6 to (R)-1 a and (S)-1 a, (R)-and (S)-enantioselective enzyme cascades for deaminationdecarboxylation-epoxidation-hydrolysis-oxidation-transamination were developed. The engineered E. coli strains produced (R)-1 a and (S)-1 a in high ee at 576 mg/L and 356 mg/L, respectively, from L-phenylalanine 6, as the first synthesis of these compounds from a bio-based chemical. Finally, L-phenylalanine biosynthesis pathway was combined with (R)-or (S)-enantioselective cascade in one strain or coupled strains, to achieve the first synthesis of (R)-1 a and (S)-1 a from a renewable feedstock. The coupled strain approach enhanced the production, affording 274 and 384 mg/L (R)-1 a and 274 and 301 mg/L (S)-1 a, from glucose and glycerol, respectively. The developed methods could be potentially useful to produce these high-value chemicals from cheap starting materials and renewable feedstocks in a green and sustainable manner.

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Resolution of racemic cis-1-amino-2-indanol by diastereomeric salt formation with (S)-2-phenylpropionic acid

Cited by 23 publications

References 7 publications

Separation of the Mixtures of Chiral Compounds by Crystallization

Separation of the Mixtures of Chiral Compounds by Crystallization

Enantioselective Cascade Biocatalysis for Deracemization of Racemic β‐Amino Alcohols to Enantiopure (S)‐β‐Amino Alcohols by Employing Cyclohexylamine Oxidase and ω‐Transaminase

Bioproduction of Enantiopure (R)‐ and (S)‐2‐Phenylglycinols from Styrenes and Renewable Feedstocks

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