Application of Threonine Aldolases for the Asymmetric Synthesis of α‐Quaternary α‐Amino Acids. Issue 16 (4th July 2018)

• Record Type: Journal Article
• Authors: Blesl, Julia; Trobe, Melanie; Anderl, Felix; Breinbauer, Rolf; Strohmeier, Gernot A.; Fesko, Kateryna
• Is Part Of: ChemCatChem. Volume 10:Issue 16(2018)
• Page Start: 3453
• Page End: 3458
• Publication Date: 2018-07-04
• Subjects: Amino acids -- Asymmetric catalysis -- Enzyme catalysis -- Quaternary stereogenic centers -- Threonine aldolases; Catalysis -- Periodicals; 541.39505
• DOI: 10.1002/cctc.201800611
• Languages: English
• ISSNs: 1867-3880

Abstract

Abstract: We report the synthesis of diverse β‐hydroxy‐α, α‐dialkyl‐α‐amino acids with perfect stereoselectivity for the α‐quaternary center through the action of l ‐ and d ‐specific threonine aldolases. A wide variety of aliphatic and aromatic aldehydes were accepted by the enzymes and conversions up to >80 % were obtained. In the case of d ‐selective threonine aldolase from Pseudomonas sp., generally higher diastereoselectivities were observed. The applicability of the protocol was demonstrated by performing enzymatic reactions on preparative scale. Using the d ‐threonine aldolase from Pseudomonas sp., (2 R, 3 S )‐2‐amino‐3‐(2‐fluorophenyl)‐3‐hydroxy‐2‐methylpropanoic acid was generated in preparative amounts in one step with a diastereomeric ratio >100 favoring the syn ‐product. A Birch‐type reduction enabled the reductive removal of the β‐hydroxy group from (2 S )‐2‐amino‐3‐hydroxy‐2‐methyl‐3‐phenylpropanoic acid to generate enantiopure l ‐α‐methyl‐phenylalanine via a two‐step chemo‐enzymatic transformation. Abstract : Just one more step : The direct biocatalytic assembly of β‐hydroxy‐α, α‐dialkyl‐α‐amino acids is outlined. Through the application of l ‐ or d ‐selective threonine aldolases with donor specificities beyond glycine, a wide variety of amino acid products can be created in a single step.