Whole-Cell Biocatalyst for Chemoenzymatic Total Synthesis of Rivastigmine
Abstract
:1. Introduction
2. Results and Discussion
2.1. Bioreduction of Prochiral Ketones 1 and 2 with Baker’s Yeast RC
2.2. Bioreduction of Ketones 1 and 2 with Lactobacillus reuteri DSM 20016 Whole Cells
2.3. Chemoenzymatic Total Synthesis of (S)-Rivastigmine
3. Materials and Methods
3.1. General Methods
3.2. Microorganisms and Media
3.3. Blank Experiments
3.4. Bioreduction of Acetophenones 1,2 by Using Baker’s Yeat Cells in Acqueous DESs Mixtures (the General Procedure Described Refers to a ChCl/Gly (1:2 mol/mol) + 10 w% Water Mixture)
3.5. Bioreduction of Ketone 2 by Using Lactobacillus reuteri Growing Cells (Table 2, Entry 2)
3.6. Bioreduction of Acetophenones 1,2 by Using Lactobacillus reuteri Resting Cells: General Procedure (Table 2)
3.7. Bioreduction of Acetophenones 1,2 by Using Lactobacillus reuteri Resting Cells in Bioreactor: General Batch Procedure (Table 2, Entries 7,8)
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Entry | Ketone | t (h) | Reaction Medium | Product (Yield %) 2 | ee (%) 3 | Absolute Configuration 4 |
---|---|---|---|---|---|---|
1 | 1 | 15 | H2O | 3 (5) 5 | N.D. | N.D. |
2 | 1 | 24 | H2O | 3 (8) 5 | N.D. | N.D. |
3 | 1 | 40 | H2O | 3 (25) | >98 | S |
4 | 1 | 120 | H2O | 3 (27) | 98 | S |
5 | 1 | 120 | ChCl/Gly 2:1 | N.R. | N.D. | N.D. |
6 | 1 | 120 | L-(+)-lactic acid/ChCl 2:1 | N.R. | N.D. | N.D. |
7 | 1 | 120 | ChCl/D-fructose 2:1 | N.R. | N.D. | N.D. |
8 | 1 | 120 | ChCl/Gly 2:1 + 10 w% H2O | N.R. | N.D. | N.D. |
9 | 1 | 120 | L-(+)-lactic acid/ChCl 2:1 + 10 w% H2O | N.R. | N.D. | N.D. |
10 | 1 | 120 | ChCl/D-fructose 2:1 + 10 w% H2O | N.R. | N.D. | N.D. |
11 | 1 | 120 | ChCl/Gly 2:1 + 20 w% H2O | 3 (8) | >98 | S |
12 | 1 | 120 | ChCl/Gly 2:1 + 40 w% H2O | 3 (32) | >98 | S |
13 | 2 | 24 | H2O | 4 (12) | >98 | S |
14 | 2 | 120 | ChCl/Gly 2:1 + 20 w% H2O | 4 (5) | 95 | S |
Entry | Ketone | t (h) | Reaction Medium | Cells Concentration(g CDW/L) | Product (Yield %) 2 | ee (%) 3 | Absolute Configuration 4 |
---|---|---|---|---|---|---|---|
1 | 2 | 24 | PBS | 1.1 (RC) | 4 (60) | 98 | R |
2 | 2 | 24 | MRS | 1.1 (GC) 1 | 4 (47) | 98 | R |
3 | 2 | 48 | PBS | 1.1 (RC) | 4 (64) | 98 | R |
4 | 2 | 72 | PBS | 1.1 (RC) | 4 (74) | 98 | R |
5 | 1 | 72 | PBS | 1.1 (RC) | 3 (16) | >98 | R |
6 | 2 | 72 | PBS | 1.1 (RC) 5 | 4 (68) | 98 | R |
7 | 2 | 72 | PBS | 1.1 (RC) 6 | 4 (71) | 98 | R |
8 | 2 | 72 | PBS | 1.1 (RC) 7 | 4 (63) | 98 | R |
9 | 2 | 24 | PBS | 4.4 (RC) | 4 (90) | 98 | R |
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Vitale, P.; Perna, F.M.; Agrimi, G.; Pisano, I.; Mirizzi, F.; Capobianco, R.V.; Capriati, V. Whole-Cell Biocatalyst for Chemoenzymatic Total Synthesis of Rivastigmine. Catalysts 2018, 8, 55. https://doi.org/10.3390/catal8020055
Vitale P, Perna FM, Agrimi G, Pisano I, Mirizzi F, Capobianco RV, Capriati V. Whole-Cell Biocatalyst for Chemoenzymatic Total Synthesis of Rivastigmine. Catalysts. 2018; 8(2):55. https://doi.org/10.3390/catal8020055
Chicago/Turabian StyleVitale, Paola, Filippo Maria Perna, Gennaro Agrimi, Isabella Pisano, Francesco Mirizzi, Roberto Vito Capobianco, and Vito Capriati. 2018. "Whole-Cell Biocatalyst for Chemoenzymatic Total Synthesis of Rivastigmine" Catalysts 8, no. 2: 55. https://doi.org/10.3390/catal8020055