scholarly journals Optimization of a Catalytic Chemoenzymatic Tandem Reaction for the Synthesis of Natural Stilbenes in Continuous Flow

Catalysts ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1404
Author(s):  
Florian Lackner ◽  
Katharina Hiebler ◽  
Bianca Grabner ◽  
Heidrun Gruber-Woelfler

In view of the development of efficient processes for the synthesis of high-value compounds, the combination of bio- and chemocatalysis is highly promising. In addition, implementation of immobilized catalysts into continuous setups allows a straightforward separation of the target compound from the reaction mixture and ensures uniform product quality. In this work, we report the optimization of a chemoenzymatic tandem reaction in continuous flow and its extended application for the synthesis of pharmacologically active resveratrol and pterostilbene. The tandem reaction involves enzymatic decarboxylation of coumaric acid employing encapsulated phenolic acid decarboxylase from B. subtilis and a Heck coupling of the obtained vinylphenol with an aryl iodide using heterogeneous Pd-Ce-Sn oxides implemented in a packed bed reactor. By optimization of the reaction conditions for the limiting cross-coupling step, the yield of (E)-4-hydroxystilbene using the fully continuous setup could be more than doubled compared to previous work. Furthermore, the improved chemoenzymatic cascade could also be applied to the synthesis of resveratrol and pterostilbene in a continuous fashion. Leaching of the metal catalyst at high temperatures limited the process in many perspectives. Therefore, the feasibility of a reactor setup with reversed flow was experimentally evaluated and approved.

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Kashyap Kumar Dubey ◽  
Dhirendra Kumar ◽  
Punit Kumar ◽  
Shafiul Haque ◽  
Arshad Jawed

Bioconversion of colchicine into its pharmacologically active derivative 3-demethylated colchicine (3-DMC) mediated by P450BM3 enzyme is an economic and promising strategy for the production of this inexpensive and potent anticancer drug. Continuous stirred tank reactor (CSTR) and packed-bed reactor (PBR) of 3 L and 2 L total volumes were compared for the production of 3-demethylated colchicine (3-DMC) a colchicine derivative using Bacillus megaterium MTCC*420 under aerobic conditions. Statistical optimization technique was utilized with the most significant variables, that is, dissolved oxygen (DO), colchicine concentration, and process time for optimization. The validation of the model was performed by experiments on the predicted values in an individual run, and the optimum parameters were DO (~50%), colchicine concentration (7.5 g/L), and process time (39 h) resulted in a maximum bioconversion of 3-DMC 3.36 g/L. The PBR reactor achieved much higher productivity (6.58 g/L/h) as reported by earlier researchers. This is the first report on the use of PBR for bioconversion of colchicine.


2018 ◽  
Vol 54 (7) ◽  
pp. 825-828 ◽  
Author(s):  
M. B. Johansen ◽  
A. T. Lindhardt

A simple to prepare, dry and handle packed bed reactor carrying CsF on CaF2, towards nucleophilic fluorinations in continuous flow, is reported.


2018 ◽  
Vol 38 (2) ◽  
pp. 270-276 ◽  
Author(s):  
Izabela R. C. Araujo ◽  
Simone D. Gomes ◽  
Tamiris U. Tonello ◽  
Shaiane Dal'Maso Lucas ◽  
Angelo G. Mari ◽  
...  

2019 ◽  
Vol 10 (1) ◽  
pp. 259-270
Author(s):  
Katharina Hiebler ◽  
Carina Dertnig ◽  
Sebastian Soritz ◽  
Manuel C. Maier ◽  
Theresa R. Hörmann ◽  
...  

AbstractThe active pharmaceutical ingredient sacubitril acts as a neprilysin inhibitor in the body and is administered to patients suffering from high blood pressure and chronic heart failure. In this paper, we report the development of a three-step setup for the synthesis of an advanced sacubitril precursor in continuous flow. The key transformation of our cascade is a Suzuki-Miyaura coupling facilitated by a heterogeneous palladium catalyst. Its implementation in a packed-bed reactor and the application of continuous flow methodologies allow intensification of the cross-coupling reaction compared to batch processing. The subsequent steps for the synthesis of the target molecule involve Boc-deprotection as well as N-succinylation, which have been optimized using the statistical “Design of Experiments” (DoE) approach. In this way, the individual as well as interactive effects of selected parameters on the output of the reactions could be investigated very efficiently. The consecutive performance of the three reaction steps using an integrated setup enabled the synthesis of a late-stage sacubitril precursor in continuous flow with 81% overall yield.


Author(s):  
Tomohiro Ichitsuka ◽  
Tatsuya Fujii ◽  
Marina Kobune ◽  
Takashi Makino ◽  
Shin-Ichiro Kawasaki

We report a continuous flow process for biaryls consisting of a packed-bed reactor and a rapid extraction system. Continuous extraction with supercritical carbon dioxide (scCO2) was applied to a Suzuki–Miyaura...


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