A Multidisciplinary Approach Toward the Rapid and Preparative-Scale Biocatalytic Synthesis of Chiral Amino Alcohols: A Concise Transketolase-/ω-Transaminase-Mediated Synthesis of (2S,3S)-2-Aminopentane-1,3-diol

Chiral amino alcohols are prevalent synthons in pharmaceuticals and synthetic bioactive compounds. The efficient synthesis of chiral amino alcohols using ammonia as the sole amino donor under mild conditions is highly desired and challenging in organic chemistry and biotechnology. Our previous work explored a panel of engineered amine dehydrogenases (AmDHs) derived from amino acid dehydrogenase (AADH), enabling the one-step synthesis of chiral amino alcohols via the asymmetric reductive amination of α-hydroxy ketones. Although the AmDH-directed asymmetric reduction is in a high stereoselective manner, the activity is yet fully excavated. Herein, an engineered AmDH derived from a leucine dehydrogenase from Sporosarcina psychrophila (SpAmDH) was recruited as the starting enzyme, and the combinatorial active-site saturation test/iterative saturation mutagenesis (CAST/ISM) strategy was applied to improve the activity. After three rounds of mutagenesis in an iterative fashion, the best variant wh84 was obtained and proved to be effective in the asymmetric reductive amination of 1-hydroxy-2-butanone with 4-fold improvements in kcat/Km and total turnover number (TTN) values compared to those of the starting enzyme, while maintaining high enantioselectivity (ee >99%) and thermostability (T5015 >53°C). In preparative-scale reaction, the conversion of 100 and 200 mM 1-hydroxy-2-butanone catalyzed by wh84 was up to 91–99%. Insights into the source of an enhanced activity were gained by the computational analysis. Our work expands the catalytic repertoire and toolbox of AmDHs.

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Chiral amino alcohols derived from (S)-6-chloronicotine as catalysts for asymmetric synthesis

Tetrahedron Letters ◽

10.1016/j.tetlet.2009.02.012 ◽

2009 ◽

Vol 50 (16) ◽

pp. 1806-1808 ◽

Cited By ~ 14

Author(s):

Sonja S. Capracotta ◽

Daniel L. Comins

Keyword(s):

Asymmetric Synthesis ◽

Amino Alcohols ◽

Chiral Amino Alcohols

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Bile acid amides derived from chiral amino alcohols: novel antimicrobials and antifungals

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2003.11.018 ◽

2004 ◽

Vol 14 (3) ◽

pp. 773-777 ◽

Cited By ~ 38

Author(s):

BrajaG. Hazra ◽

VandanaS. Pore ◽

SanjeevKumar Dey ◽

Suchitra Datta ◽

MahendraP. Darokar ◽

...

Keyword(s):

Bile Acid ◽

Amino Alcohols ◽

Chiral Amino Alcohols

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Cover Picture: A Theoretical Study of the Mechanism of the Desymmetrization of Cyclic meso-Anhydrides by Chiral Amino Alcohols (ChemCatChem 9/2010)

ChemCatChem ◽

10.1002/cctc.201090035 ◽

2010 ◽

Vol 2 (9) ◽

pp. 1017-1017

Author(s):

Burcu Dedeoglu ◽

Saron Catak ◽

K. N. Houk ◽

Viktorya Aviyente

Keyword(s):

Theoretical Study ◽

Amino Alcohols ◽

Chiral Amino Alcohols

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Circular dichroism spectra of tetraamminecobalt(III) complexes of amino alcohols

Australian Journal of Chemistry ◽

10.1071/ch9782399 ◽

1978 ◽

Vol 31 (11) ◽

pp. 2399 ◽

Cited By ~ 3

Author(s):

CJ Hawkins ◽

GA Lawrance ◽

JA Palmer

Keyword(s):

Circular Dichroism ◽

Chemical Shift ◽

Chemical Shifts ◽

Amino Alcohols ◽

Circular Dichroism Spectra ◽

Chemical Shift Difference ◽

Solvent Dependence ◽

Cotton Effects ◽

Circular Dichroïsm ◽

Chiral Amino Alcohols

The circular dichroism spectra are reported for tetraamminecobalt(III) complexes with the chiral amino alcohols 2-aminopropan-1-ol, 2- aminobutan-1-ol, 1-aminopropan-2-ol, 2-amino-1-phenyl-ethanol, ψ- ephedrine and ephedrine with the alcohol groups protonated (OH) and deprotonated (O-). The solvent dependence of the chemical shifts of the NH protons was investigated to determine the effects of stereoselective solvation on the circular dichroism, but, in contrast to some other related systems, the chemical shift difference between the two NH2 protons was relatively insensitive to solvent. Consistent with this, the circular dichroism spectra of the tetraphenylborate salts of the deprotonated complexes were found not to be markedly dependent on solvent. Tetraammine-{(-)-ψ-ephedrine)cobalt(III) and tetraammine{(-)- ephedrine}cobalt(III) were found to have the same signs of Cotton effects for the various d-d transitions, whereas bis{(-)-ψ- ephedrine}copper(II) and bis{(-)-ephedrine}copper(II) had opposite signs. This has been explained in terms of different conformer populations in the cobalt(III) and copper(II) systems.

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