Markedly improving Novozym 435-mediated regioselective acylation of 1-beta-D-arabinofuranosylcytosine by using co-solvent mixtures as the reaction media.
A comparative study was made of Novozym 435-catalyzed regioselective acylation of 1-beta-D-arabinofuranosylcytosine with vinyl propionate for the preparation of the 5'-O-monoester in eleven co-solvent mixtures and three pure polar solvents. Novozym 435 displayed low or no acylation activity toward 1-beta-D-arabinofuranosylcytosine in pure polar solvents, although those solvents can dissolve the nucleosides well. When a hexane-pyridine co-solvent system was adopted, both the initial rate and the substrate conversion were enhanced markedly. The polarity of co-solvent mixtures had significant effect on the reaction. Among the solvent mixtures investigated, the higher the polarity of the solvent mixture, the lower the initial reaction rate and the substrate conversion. It was also found that the acylation was dependent on the hydrophobic solvent content, the water activity and the reaction temperature. The most suitable co-solvent, initial water activity, and reaction temperature were hexane-pyridine (28:72, v/v), 0.07, and 50 degrees C, respectively. Under these conditions, the initial rate, the substrate conversion and the regioselectivity were as high as 91.1 mM h(-1), >97% and >98%, respectively, after a reaction time of 6 h. Among the reaction mediums examined, the lowest apparent activation energy was achieved with hexane-pyridine (28:72, v/v), in which Novozym 435 also exhibited good thermal stability.
Li
Xiao-Feng
XF
College of Biological Sciences & Biotechnology, South China University of Technology, Guangzhou 510640, China.
Zong
Min-Hua
MH
Wu
Hong
H
Lou
Wen-Yong
WY
D000215:Acylation; D045424:Complex Mixtures / Q000737:chemistry; D003561:Cytarabine / Q000032:analysis / Q000737:chemistry*; D004789:Enzyme Activation; D004795:Enzyme Stability; D004800:Enzymes, Immobilized; D005656:Fungal Proteins; D008049:Lipase / Q000032:analysis / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry*
D045424:Complex Mixtures; D004800:Enzymes, Immobilized; D005656:Fungal Proteins; D012997:Solvents; D003561:Cytarabine; C093667:Novozyme 435; D008049:Lipase