Efficiently enhancing regioselective acylation of 5-azacytidine catalysed by Candida antarctica lipase B with co-solvent mixtures as the reaction media.
A comparative study of regioselective acylation of 5-azacytidine catalysed by CAL-B (Candida antarctica lipase B) in co-solvent mixtures and in pure organic solvents was performed, to our knowledge for the first time, and it was shown that a remarkable enhancement in the initial rate and substrate conversion in the reaction could be achieved with co-solvents as the reaction medium instead of pure organic solvents. For the CAL-B-catalysed regioselective synthesis of 5'-O-butyryl-5-azacytidine in co-solvent mixtures, the optimal conditions were as follows: optimal co-solvent mixture, hexane/pyridine (40/60, v/v); initial aw (water activity), 0.07; enzyme dosage, 50 units/ml; vinyl butyrate/5-azacytidine molar ratio, 15:1; temperature, 60 °C. Under the optimal conditions, v0 (the initial reaction rate), C (the substrate conversion) and the regioselectivity of the reaction were 0.75 mM/min, 99.0% and above 99% respectively. Similar phenomena were observed in the CAL-B-catalysed regioselective acylation of 5-azacytidine with an extensive range of fatty acid vinyl esters (from C2 to C18). Compared with pure pyridine, the reactions were greatly accelerated in a hexane/pyridine (40/60, v/v) co-solvent mixture and 5-azacytidine could be biotransformed into its derivative 5'-O-acyl-5-azacytidine at a much higher conversion rate (91.4-99.0% as against 40.2-43.5%). Meanwhile, adoption of a co-solvent mixture as the reaction medium could also greatly lower the enzyme dosage and the molar ratio of acyl donor to 5-azacytidine.
Wu
Hong
H
Zong
Minhua
M
Chen
Xiyu
X
D001374:Azacitidine / Q000737:chemistry* / Q000378:metabolism*; D002087:Butyrates; D005656:Fungal Proteins / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D008049:Lipase / Q000378:metabolism*; D012997:Solvents; D013237:Stereoisomerism; D013696:Temperature; D014753:Vinyl Compounds
D002087:Butyrates; D005656:Fungal Proteins; D012997:Solvents; D014753:Vinyl Compounds; C095498:vinyl butyrate; D008049:Lipase; C431349:lipase B, Candida antarctica; D001374:Azacitidine