One-Pot Enzymatic Synthesis of Enantiopure 1,3-Oxathiolanes Using Trichosporon laibachii Lipase and the Kinetic Model

Abstract

The dynamic covalent kinetic resolution protocol was efficiently used for the synthesis of the enantiopure ((R)-5acetoxy-1,3-oxathiolan-2-yl)ethyl benzoate (P R ) from substrates 2-(phenylmethoxy)acetaldehyde (A), 1,4-dithiane-2,5-diol (B), and phenyl acetate (D) by a one-pot process with 99.6% conversion, 97.3% yield, and 96.5% ee through the combination of reversible hemithioacetal transformation and enantiomer-selective lactonization catalyzed by immobilized lipase from Trichosporon laibachii. A proposed kinetic model consisting of transformation and lactonization was developed herein for the first time, fitting the experimental data very well. It was concluded that (1) the transformation in a chemical fashion may follow a power law. (2) The enzymatic lactonization may follow a sequential mechanism with product inhibition. The reaction kinetic data reveal that phenol (P 1 ) would have strong product inhibition, while noncompetitive inhibition, product inhibition of P R , and substrate inhibition were not recognized. The model suggests that there is a common limitation of both enzyme and chemistry in the chemo-enzymatic system, and thus the amount of lipase was increased to accelerate the enzymatic lactonization and to reduce the limitation caused by the enzymatic reaction, resulting in the increase of the yield of P R significantly. The experimental results demonstrate that both the internal and external mass diffusion resistance could be negligible, and thus the kinetic model developed is the inherent kinetic one.

Selective hydrogenation of α‐pinene on a nickel supported aluminophosphate catalyst: Process optimization and reaction kinetics

“…For an intrinsic kinetic study, the effect of diffusion must be eliminated. The external diffusion could be eliminated by enhancing the stirring rate and the internal diffusion could be eliminated by reducing the particle size of the catalyst 42 …”

Asymmetric Sulfoxidation of Thioether Catalyzed by Soybean Pod Shell Peroxidase to Form Enantiopure Sulfoxide in Water‐in‐Oil Microemulsions: A Kinetic Model

“…There are many studies on the mechanism of the lipase‐catalyzed reaction, but a few on peroxidase. It is generally believed that many reactions catalyzed by enzymes obey one of the following two mechanisms: (1) Ping‐pong mechanism [23] and (2) Sequential mechanism [24–26] . The oxidation of sulfides catalyzed by peroxidase to enantiopure sulfoxides involves two intermediate forms of peroxidase: compounds I and II, which can actually be thought of as changing patterns of the peroxidase.…”

“…With the experimental data of asymmetric sulfoxidation of the thioether to form the enantiopure sulfoxide, in order to identify the kinetic model, the kinetic model parameters of equations 8–23 were estimated using coupling ordinary differential equations solver with an optimization method, and the kinetic model was used to fit the kinetic experimental data by the minimum of the equation : [24] …”

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

“…As compared to nearly all of the lipase-catalyzed methods to produce the chiral oxathiolane precursor 68 of lamivudine (1) from a mixture of isomers, i.e., 67, the reaction occurred in a single-phase aqueous system, which may be considered a green chemistry approach. Recently, Zhang and co-workers [63] developed a one-pot enzymatic synthesis of enantiopure 1,3-oxathiolane with Trichosporon laibachii lipase and a kinetic resolution. The synthesis of enantiopure ((R)-5-acetoxy-1,3-oxathiolan-2-yl)methyl benzoate (71) was carried out from the substrates 3a, 1,4dithiane-2,5-diol (3q), and phenyl acetate via dynamic covalent kinetic resolution.…”

“…Recently, Zhang and co-workers [ 63 ] developed a one-pot enzymatic synthesis of enantiopure 1,3-oxathiolane with Trichosporon laibachii lipase and a kinetic resolution. The synthesis of enantiopure (( R )-5-acetoxy-1,3-oxathiolan-2-yl)methyl benzoate ( 71 ) was carried out from the substrates 3a , 1,4-dithiane-2,5-diol ( 3q ), and phenyl acetate via dynamic covalent kinetic resolution.…”