title: Regioselective synthesis of cytarabine monopropionate by using a fungal whole-cell biocatalyst in nonaqueous medium.
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.
authors: State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, Guangzhou 510641, China.
authors: Mei-yan
authors: MY
authors: Yang
authors: College of Light Industry and Food Sciences, South China University of Technology, Wushan Road 381, Guangzhou 510641, China.
authors: Hui
authors: H
authors: Wu
authors: College of Light Industry and Food Sciences, South China University of Technology, Wushan Road 381, Guangzhou 510641, China.
authors: Zhi-hong
authors: ZH
authors: Lu
authors: State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, Guangzhou 510641, China; College of Light Industry and Food Sciences, South China University of Technology, Wushan Road 381, Guangzhou 510641, China. Electronic address: xflibio@gmail.com.
authors: Xiao-feng
authors: XF
authors: Li
authors: State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, Guangzhou 510641, China; College of Light Industry and Food Sciences, South China University of Technology, Wushan Road 381, Guangzhou 510641, China.
authors: Fu-rao
authors: FR
authors: Lai
authors: State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, Guangzhou 510641, China. Electronic address: zhaoguanglei@gmail.com.
authors: Guang-lei
authors: GL
authors: Zhao
mesh_terms: D001236:Aspergillus oryzae / Q000166:cytology / Q000378:metabolism*; D055162:Biocatalysis; D003561:Cytarabine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D013237:Stereoisomerism; D014753:Vinyl Compounds / Q000737:chemistry / Q000378:metabolism*
chemical_list: D014753:Vinyl Compounds; D003561:Cytarabine
keywords: Acylation; Fungal whole-cell; Nucleoside; Regioselectivity; Solvent engineering