An Enzymatic Flow-Based Preparative Route to Vidarabine
Abstract
:1. Introduction
2. Results and Discussion
2.1. Immobilization on Glyoxyl–Agarose under Continuous Flow
2.2. Transglycosylation Reaction Using Glyoxyl–Agarose-Based CpUP/AhPNP-Bioreactor
2.3. Co-Immobilization on EziGTM Carriers in Continuous Flow
2.4. Continuous Flow Synthesis of Ara-A (11) and Product Isolation
3. Materials and Methods
3.1. Analytical Methods
3.2. Immobilization Yields
3.3. Co-Immobilization of CpUP and AhPNP on Glyoxyl–Agarose under Flow Conditions
3.4. Co-Immobilization of CpUP and AhPNP on EziGTM1 (Opal) under Flow Conditions
3.5. Standard Activity Assay of CpUP
3.6. Standard Activity Assay of AhPNP
3.7. Flow Activity Assay of AhPNP
3.8. Flow Activity Assay of CpUP
3.9. General Procedure for the Flow Transglycosylation Reaction
3.10. Synthesis of Vidarabine (11)
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of vidarabine are available from the authors. |
Entry | Residence Time (min) | [Urd, 1] (mM) | [Ade, 5] (mM) | Conversion (%) a |
---|---|---|---|---|
1 | 5 | 4 | 2 | 85 |
2 | 5 | 8 | 4 | 86 |
3 | 10 | 8 | 4 | 84 |
4 | 20 | 8 | 4 | 84 |
5 | 5 | 16 | 8 | 86 |
6 | 2.5 | 16 | 8 | 86 |
7 | 1 | 16 | 8 | 86 |
8 b | 5 | 32 | 16 | 88 |
9 b | 5 | 40 | 20 | 89 |
10 c | 5 | 100 | 50 | 89 |
Residence Time (min) | Conversion (%) | Space Time Yield (g/day) | Catalyst Productivity (24 h) (mmolproduct/mgenzyme) |
---|---|---|---|
1 | 85 | 1.8 | 0.98 |
Sugar Donor | Sugar Acceptor | Product | Conversion a (%) |
---|---|---|---|
1 (Urd) | 5 (Ade) | 7 (Ado) | 76 |
1 (Urd) | 6 (Hpx) | 9 (Ino) | 45 |
2 (dUrd) | 5 (Ade) | 8 (dAdo) | 70 |
2 (dUrd) | 6 (Hpx) | 10 (dIno) | 50 |
3 (Thd) | 5 (Ade) | 8 (dAdo) | 73 |
3 (Thd) | 6 (Hpx) | 10 (dIno) | 40 |
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Tamborini, L.; Previtali, C.; Annunziata, F.; Bavaro, T.; Terreni, M.; Calleri, E.; Rinaldi, F.; Pinto, A.; Speranza, G.; Ubiali, D.; et al. An Enzymatic Flow-Based Preparative Route to Vidarabine. Molecules 2020, 25, 1223. https://doi.org/10.3390/molecules25051223
Tamborini L, Previtali C, Annunziata F, Bavaro T, Terreni M, Calleri E, Rinaldi F, Pinto A, Speranza G, Ubiali D, et al. An Enzymatic Flow-Based Preparative Route to Vidarabine. Molecules. 2020; 25(5):1223. https://doi.org/10.3390/molecules25051223
Chicago/Turabian StyleTamborini, Lucia, Clelia Previtali, Francesca Annunziata, Teodora Bavaro, Marco Terreni, Enrica Calleri, Francesca Rinaldi, Andrea Pinto, Giovanna Speranza, Daniela Ubiali, and et al. 2020. "An Enzymatic Flow-Based Preparative Route to Vidarabine" Molecules 25, no. 5: 1223. https://doi.org/10.3390/molecules25051223