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4 Publications visible to you, out of a total of 4
Aldolase-Catalyzed Asymmetric Synthesis of N-Heterocycles by Addition of Simple Aliphatic Nucleophiles to Aminoaldehydes

Abstract (Expand)

Nitrogen heterocycles are structural motifs found in many bioactive natural products and of utmost importance in pharmaceutical drug development. In this work, a stereoselective synthesis of functionalized … N‐heterocycles was accomplished in two steps, comprising the biocatalytic aldol addition of ethanal and simple aliphatic ketones such as propanone, butanone, 3‐pentanone, cyclobutanone, and cyclopentanone to N‐Cbz‐protected aminoaldehydes using engineered variants of d‐fructose‐6‐phosphate aldolase from Escherichia coli (FSA) or 2‐deoxy‐d‐ribose‐5‐phosphate aldolase from Thermotoga maritima (DERATma) as catalysts. FSA catalyzed most of the additions of ketones while DERATma was restricted to ethanal and propanone. Subsequent treatment with hydrogen in the presence of palladium over charcoal, yielded low‐level oxygenated N‐heterocyclic derivatives of piperidine, pyrrolidine and N‐bicyclic structures bearing fused cyclobutane and cyclopentane rings, with stereoselectivities of 96–98 ee and 97:3 dr in isolated yields ranging from 35 to 79%.

Authors: Raquel Roldán, Karel Hernández, Jesús Joglar, Jordi Bujons, Teodor Parella, Wolf-Dieter Fessner, Pere Clapés

Date Published: 6th Jun 2019

Publication Type: Not specified

One‐Pot Cascade Synthesis of (3S)‐Hydroxyketones Catalyzed by Transketolase via Hydroxypyruvate Generated in Situ from d‐Serine by d‐Amino Acid Oxidase

Abstract (Expand)

We described an efficient in situ generation of hydroxypyruvate from d‐serine catalyzed by a d‐amino acid oxidase from Rhodotorula gracilis. This strategy revealed an interesting alternative to the … conventional chemical synthesis of hydroxypyruvate starting from toxic bromopyruvate or to the enzymatic transamination from l‐serine requiring an additional substrate as amino acceptor. Hydroxypyruvate thus produced was used as donor substrate of transketolases from Escherichia coli or from Geobacillus stearothermophilus catalyzing the stereoselective formation of a carbon−carbon bond. The enzymatic cascade reaction was performed in one‐pot in the presence of d‐serine and appropriate aldehydes for the synthesis of valuable (3S)‐hydroxyketones, which were obtained with high enantio‐ and diastereoselectivity and in good yield. The efficiency of the process was based on the irreversibility of both reactions allowing complete conversion of d‐serine and aldehydes.

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Date Published: 6th Jun 2019

Publication Type: Not specified

Second-Generation Engineering of a Thermostable Transketolase (TK Gst ) for Aliphatic Aldehyde Acceptors with Either Improved or Reversed Stereoselectivity

Abstract (Expand)

The transketolase from Geobacillus stearothermophilus (TKGst) is a thermostable enzyme with notable high activity and stability at elevated temperatures, but it accepts non‐α‐hydroxylated aldehydes … only with low efficiency. Here we report a protein engineering study of TKGst based on double‐site saturation mutagenesis either at Leu191 or at Phe435 in combination with Asp470; these are the residues responsible for substrate binding in the active site. Screening of the mutagenesis libraries resulted in several positive variants with activity towards propanal up to 7.4 times higher than that of the wild type. Variants F435L/D470E and L191V/D470I exhibited improved (73 % ee, 3S) and inverted (74 % ee, 3R) stereoselectivity, respectively, for propanal. L191V, L382F/E, F435L, and D470/D470I were concluded to be positive mutations at Leu191, Leu382, Phe435, and Asp470 both for activity and for stereoselectivity improvement. These results should benefit further engineering of TKGst for various applications in asymmetric carboligation.

Authors: Chaoqiang Zhou, Thangavelu Saravanan, Marion Lorillière, Dongzhi Wei, Franck Charmantray, Laurence Hecquet, Wolf-Dieter Fessner, Dong Yi

Date Published: 2nd Mar 2017

Publication Type: Not specified

Diastereoselective synthesis of vicinal amino alcohols

Abstract (Expand)

The vicinal amino alcohol is a common motif in natural products and pharmaceuticals. Amino acidsconstitute a natural, inexpensive, and enantiopure choice of starting material for the synthesis of … suchfunctionalities. However, the matters concerning diastereoselectivity are not obvious. This Perspectivetakes a look in thefield of diastereoselective synthesis of vicinal amino alcohols starting from amino acidsusing various methods. https://pubs.rsc.org/en/content/articlepdf/2012/ob/c2ob25357g

Authors: Oskari K. Karjalainen, Ari M. P. Koskinen

Date Published: 2012

Publication Type: Not specified

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