Biocatalytic Parallel Interconnected Dynamic Asymmetric Disproportionation of α-Substituted Aldehydes: Atom-Efficient Access to Enantiopure ( S )-Profens and Profenols.

Autor: Tassano E; Department of Chemistry University of Graz Heinrichstrasse 28 8010 Graz Austria., Faber K; Department of Chemistry University of Graz Heinrichstrasse 28 8010 Graz Austria., Hall M; Department of Chemistry University of Graz Heinrichstrasse 28 8010 Graz Austria.
Jazyk: angličtina
Zdroj: Advanced synthesis & catalysis [Adv Synth Catal] 2018 Jul 16; Vol. 360 (14), pp. 2742-2751. Date of Electronic Publication: 2018 Jun 12.
DOI: 10.1002/adsc.201800541
Abstrakt: The biocatalytic asymmetric disproportionation of aldehydes catalyzed by horse liver alcohol dehydrogenase (HLADH) was assessed in detail on a series of racemic 2-arylpropanals. Statistical optimization by means of design of experiments (DoE) allowed the identification of critical interdependencies between several reaction parameters and revealed a specific experimental window for reaching an 'optimal compromise' in the reaction outcome. The biocatalytic system could be applied to a variety of 2-arylpropanals and granted access in a redox-neutral manner to enantioenriched ( S )-profens and profenols following a parallel interconnected dynamic asymmetric transformation (PIDAT). The reaction can be performed in aqueous buffer at ambient conditions, does not rely on a sacrificial co-substrate, and requires only catalytic amounts of cofactor and a single enzyme. The high atom-efficiency was exemplified by the conversion of 75 mM of rac -2-phenylpropanal with 0.03 mol% of HLADH in the presence of ∼0.013 eq. of oxidized nicotinamide adenine dinucleotide (NAD + ), yielding 28.1 mM of ( S )-2-phenylpropanol in 96% ee and 26.5 mM of ( S )-2-phenylpropionic acid in 89% ee , in 73% overall conversion. Isolated yield of 62% was obtained on 100 mg-scale, with intact enantiopurities.
Databáze: MEDLINE
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