Regioselective synthesis of cytarabine monopropionate by using a fungal whole-cell biocatalyst in nonaqueous medium |
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| Institution: | 1. State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, Guangzhou 510641, China;2. College of Light Industry and Food Sciences, South China University of Technology, Wushan Road 381, Guangzhou 510641, China;1. Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel;2. School of Pharmacy, Institute for Drug Research, The Hebrew University of Jerusalem, Ein Karem, Jerusalem 91120, Israel;3. Faculty of Life Sciences and Institute of Nanotechnology, Bar-Ilan University, Ramat-Gan 52900, Israel;1. School of Pharmacy, Xuzhou Medical College, Xuzhou 221004, People’s Republic of China;2. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, People’s Republic of China;3. Department of Environmental Pharmacy, Tianjin Institute of Health and Environmental Medicine, Tianjin 300050, People’s Republic of China;1. Department of Chemistry & Pharmaceutical Sciences, Piazzale Europa 1, University of Trieste, 34127 Trieste, Italy;2. Molecular Simulation Engineering (MOSE) Laboratory, DI3, Piazzale Europa 1, University of Trieste, 34127 Trieste, Italy;1. Department of Biomedical Sciences, University of Sassari, Sassari, Italy;2. “G. Minardi” Laboratory of Cognitive Neuroscience, Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy |
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| Abstract: | The utilization of a dehydrated fungal biocatalyst of Aspergillus oryzae cells was successfully performed to achieve efficient acylation modification of a polar nucleoside cytarabine (ara-C). Organic solvents showed evident influence on the reaction catalyzed by the A. oryzae whole-cells. Except for hexane-pyridine, the catalytic activity and regioselectivity of the whole-cells clearly increased with increasing the polarity of the hydrophobic organic solvents used. The effects of some crucial factors on the reaction were further examined. The best reaction medium, hydrophobic solvent concentration, vinyl propionate/ara-C ratio, reaction temperature and shaking speed were confirmed as isopropyl ether (IPE)-pyridine, 30% (v/v), 90, 30 °C and 140–180 rpm, respectively. The cell biocatalyst also showed good thermal stabilities in both IPE-pyridine and hexane-pyridine systems. In addition, the desired 3′-O-propional derivative of ara-C was synthesized with the yields of 88.3% and regioselectivity (>70%). The resulting biocatalytic system appears to be an effective alternative, and can thus be employed for application in highly regioselective modification of nucleoside analogues. |
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| Keywords: | Fungal whole-cell Nucleoside Acylation Solvent engineering Regioselectivity |
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