Highly efficient regioselective synthesis of 5'-O-lauroyl-5-azacytidine catalyzed by Candida antarctica Lipase B.
Enzymatic regioselective acylation of 5-azacytidine with vinyl laurate was successfully conducted with an immobilized lipase from Candida antarctica type B (i.e., Novozym 435) for the first time. The acylation of 5-azacytidine took place at its primary hydroxyl group and the desired product 5'-O -lauroyl-5-azacytidine could be prepared with high reaction rate, high conversion, and excellent regioselectivity. The influences of several key variables on the enzymatic acylation were also systematically examined. Pyridine was found to be the best reaction medium. The optimum initial water activity, the molar ratio of vinyl laurate to 5-azacytidine and reaction temperature were 0.07, 30:1, and 50 degrees C, respectively. Under the optimized conditions described above, the initial reaction rate, the substrate conversion, and the regioselectivity were as high as 0.58 mM/min, 95.5%, and >99%, respectively, after a reaction time of around 5 h.
Chen
Xi-Yu
XY
Lab of Applied Biocatalysis, South China University of Technology, Guangzhou, 510640, China.
Zong
Min-Hua
MH
Lou
Wen-Yong
WY
Wu
Hong
H
D001374:Azacitidine / Q000138:chemical synthesis*; D002384:Catalysis; D004800:Enzymes, Immobilized / Q000737:chemistry; D005656:Fungal Proteins; D007536:Isomerism; D007848:Laurates / Q000737:chemistry*; D008049:Lipase / Q000737:chemistry*
D004800:Enzymes, Immobilized; D005656:Fungal Proteins; D007848:Laurates; C093667:Novozyme 435; D008049:Lipase; C431349:lipase B, Candida antarctica; D001374:Azacitidine