Synthesis Of Α-hydroxy Ketones Research Articles

Synthesis of α-hydroxy ketones through novel one-pot multi-enzyme cascade system from racemic epoxides

α-Hydroxy ketones, highly versatile building blocks, present challenges for their green and efficient synthesis. Based on thermodynamic analysis, a novel in vitro one-pot multi-enzyme cascade system was designed for synthesizing 2-hydroxyacetophenone (1c) from racemic styrene oxide (1a). This system incorporated a Rhodotorula paludigena epoxide hydrolase (RpEHL360V) for the enantioconvergent hydrolysis of rac-1a to (R)-phenyl-1,2-ethanediol (1b), a Bacillus subtilis (2,3)-butanediol dehydrogenase (BsBDHAI49L/V266L/G292A) for the subsequent oxidation to 1c, and a Lactobacillus casei lactate dehydrogenase (LcLDH1) for the reduction of pyruvate to lactate, thereby facilitating coenzyme recycling and shifting the reaction's thermodynamic equilibrium. After optimizing the reaction conditions, the system reached its highest efficiency using cell-free extracts of RpEHL360V (4.0 U/mL), BsBDHAI49L/V266L/G292A (0.3 U/mL), and LcLDH1 (0.1 U/mL), along with 4 mM NADH and 200 mM sodium pyruvate as cofactor and cosubstrate, respectively, in a Na2HPO4-NaH2PO4 buffer (100 mM, pH 8.0) at 30 °C. Under these conditions, the system catalyzed the conversion of 50 mM rac-1a to 1c with a total yield of 73.1 % and a maximum space-time yield of 10.7 mmol/L/h within 24 h. Furthermore, this one-pot system was applied to catalyze 20 mM of rac-4-chlorostyrene oxide and 1,2-epoxyhexane, successfully synthesizing two corresponding α‑hydroxy ketones, each with a space-time yield of 0.7 mmol/L/h, demonstrating the system's efficacy for the production of α‑hydroxy ketones.

Synthesis of α-hydroxy ketones and vicinal (R,R)-diols by Bacillus clausii DSM 8716T butanediol dehydrogenase.

α-hydroxy ketones (HK) and 1,2-diols are important building blocks for fine chemical synthesis. Here, we describe the R-selective 2,3-butanediol dehydrogenase from B. clausii DSM 8716T (BcBDH) that belongs to the metal-dependent medium chain dehydrogenases/reductases family (MDR) and catalyzes the selective asymmetric reduction of prochiral 1,2-diketones to the corresponding HK and, in some cases, the reduction of the same to the corresponding 1,2-diols. Aliphatic diketones, like 2,3-pentanedione, 2,3-hexanedione, 5-methyl-2,3-hexanedione, 3,4-hexanedione and 2,3-heptanedione are well transformed. In addition, surprisingly alkyl phenyl dicarbonyls, like 2-hydroxy-1-phenylpropan-1-one and phenylglyoxal are accepted, whereas their derivatives with two phenyl groups are not substrates. Supplementation of Mn2+ (1 mM) increases BcBDH's activity in biotransformations. Furthermore, the biocatalytic reduction of 5-methyl-2,3-hexanedione to mainly 5-methyl-3-hydroxy-2-hexanone with only small amounts of 5-methyl-2-hydroxy-3-hexanone within an enzyme membrane reactor is demonstrated.

Synthesis of α-Hydroxy Ketones from Vicinal Diols by Selective Dehydrogenation over Ir–ReOx/SiO2 Catalyst

Abstract Rhenium oxide-modified Ir/SiO2 (Ir–ReOx/SiO2) catalyst shows high activity and selectivity for the dehydrogenation of trans-1,2-cyclohexanediol to 2-hydroxycyclohexanone in water solvent under Ar. Linear vicinal diols bearing two secondary hydroxy groups or both a primary hydroxy group and a secondary hydroxy group can also be transformed to the corresponding α-hydroxy ketones in high selectivities. Ir–ReOx/SiO2 can be reused at least four times without loss of activity and selectivity.

Pd-Catalyzed Asymmetric Synthesis of α-Hydroxy Ketones, Acids and Esters

Pd-Catalyzed Asymmetric Synthesis of α-Hydroxy Ketones, Acids and Esters

Synthesis of α-Hydroxy Ketones by Using Magnetic Nanobead Copper Catalysts

Organic-inorganic hybrid polymer-encapsulated magnetic nanobeads (HP-MB) catalyst was prepared for use as a magnetically separable heterogeneous oxidation catalyst. Commercially available amino-functionalized magnetic beads 1 were mixed with Cu(BF4)2×6H2O and 4,4′-bipyridine (bpy) to form the Cu-bpy HP-MB 2 (eq. 1). The oxidation of various silyl enolates 3a-i with oxygen took place in the presence of 6 mol% of catalyst 2 to give the corresponding α-hydroxy ketones 4a-i in 75-99% yield (eq. 2). This catalyst was separated from the reaction mixture with an external magnet, and reused five times in the oxidation of 3j with no significant loss of activity (eq. 3).

Synthesis of α-hydroxyketones from 1,2-diols over Cu-based catalyst

Synthesis of α-hydroxyketones from 1,2-diols over copper catalysts modified with ZnO, Al 2O 3 and ZrO 2 was investigated. 1-Hydroxy-2-butanone was efficiently produced by the dehydrogenation of 1,2-butanediol over Cu–Zn–Zr–Al–O catalysts: the highest activity was obtained at the molar ratio of CuO:ZnO:ZrO 2:Al 2O 3 = 12:1:2:2. Several α-hydroxyketones were produced by the dehydrogenation of 1,2-diols with carbon chain of C3–C6.

Carbonylation of dialkylcyanocuprates with carbon monoxide: Synthesis of α-hydroxyketones

Dialkylcyanocuprates, prepared from copper(l) cyanide and the corresponding alkyllithium or Gringard reagents, readily react with carbon monoxide in the presence of tri- n-butylphosphine at −78 °C in THF to give α-hydroxyketones in high yields (65–85%).

Synthesis of α-hydroxy ketones using a HOF·MeCN complex

The complex, HOF·MeCN made directly by bubbling fluorine through aqueous acetonitrile, reacts quickly and efficiently with enolic forms of ketones to produce α-hydroxy ketones.