title: Biomimetic catalytic transformation of toxic α-oxoaldehydes to high-value chiral α-hydroxythioesters using artificial glyoxalase I.
abstract: Glyoxalase I plays a critical role in the enzymatic defence against glycation by catalysing the isomerization of hemithioacetal, formed spontaneously from cytotoxic α-oxoaldehydes and glutathione, to (S)-α-hydroxyacylglutathione derivatives. Upon the hydrolysis of the thioesters catalysed by glyoxalase II, inert (S)-α-hydroxy acids, that is, lactic acid, are then produced. Herein, we demonstrate highly enantioselective glyoxalase I mimic catalytic isomerization of in-situ-generated hemithioacetals, providing facile access to both enantiomers of α-hydroxy thioesters. Owing to the flexibility of thioesters, a family of optically pure α-hydroxyamides, which are highly important drug candidates in the pharmaceutical industry, were prepared without any coupling reagents. Similar to real enzymes, the enforced proximity of the catalyst and substrates by the chiral cage in situ formed by the incorporation of potassium salt can enhance the reactivity and efficiently transfer the stereochemical information.
authors.affiliation: Department of Chemistry, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon, Gyeonggi 440-746, Korea.
authors.forename: Sang Yeon
authors.identifier: 0000-0002-1368-9439
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Chemistry, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon, Gyeonggi 440-746, Korea.
authors.forename: In-Soo
authors.identifier: 0000-0001-7207-8921
authors.initials: IS
authors.lastname: Hwang
authors.affiliation: Department of Chemistry, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon, Gyeonggi 440-746, Korea.
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon, Gyeonggi 440-746, Korea.
authors.forename: Choong Eui
authors.identifier: 0000-0001-9221-6789
authors.initials: CE
authors.lastname: Song
mesh_terms: D000447:Aldehydes / Q000378:metabolism*; D032701:Biomimetics; D002384:Catalysis; D004952:Esters / Q000378:metabolism*; D007791:Lactoylglutathione Lyase / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D000447:Aldehydes; D004952:Esters; D007791:Lactoylglutathione Lyase