BACKGROUND Mitomycin C (MMC) is one of the most important members of the mitomycin family that have been widely used as a strong antineoplastic antibiotic for treating various tumors. In this study, enzymatic oxidation/amination reaction of 2‐methyl‐1,4‐hydroquinone with n‐butylamine was carried out to synthesize 2‐methyl‐3‐n‐butylaminoyl‐1,4‐benzoquinone mitomycin analogs. RESULTS A kinetic model was developed based on an ordered sequential mechanism for this cascade reaction system catalyzed by two enzymes, which revealed that the limiting step of the system was the laccase‐mediated oxidation of 2‐methyl‐3‐n‐butylaminoyl‐4‐hydro‐1‐quinone and removing the limiting step resulted in a yield increase from 88.3% to 96.7%. CONCLUSION The developed kinetic model fitted the test data very well, indicating that the reactions catalyzed by coupling of laccase with lipase might follow the ordered sequential mechanism with product inhibition. Synthesis of mitomycin analogs catalyzed by coupling of laccase with lipase has great potential for practical application. © 2020 Society of Chemical Industry

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.

No abstract

ε-Caprolactone (ε-CL) has attracted a great deal of attention and a high product concentration is of great significance for reducing production cost. The optimization of ε-CL synthesis through chemoenzymatic Baeyer-Villiger oxidation mediated by immobilized Trichosporon laibacchii lipase was studied using response surface methodology (RSM). The yield of ε-CL was 98.06% with about 1.2 M ε-CL concentration that has a substantial increase mainly due to both better stability of the cross-linked immobilized lipase used and the optimum reaction conditions in which the concentration of cyclohexanone was 1.22 M, the molar ratio of cyclohexanone:urea hydrogen peroxide (UHP) was 1:1.3, and the reaction temperature was 56.5 C. Based on our experimental results, it can be safely concluded that there are three reactions in this reaction system, not just two reactions, in which the third reaction is that the acetic acid formed reacts with UHP to form peracetic acid in situ catalyzed by the immobilized lipase. A quadratic polynomial model based on RSM experimental results was developed and the R 2 value of the equation is 0.9988, indicating that model can predict the experimental results with high precision. The experimental results also show that the molar ratio of cyclohexanone to UHP has very significant impact on the yield of ε-CL (p < .0006). K E Y W O R D SBaeyer-Villiger oxidation, caprolactone, response surface methodology, response surface optimization, Trichosporon laibacchi lipase