Efficient regioselective synthesis of 3'-O-crotonylfloxuridine catalysed by Pseudomonas cepacia lipase.
Pseudomonas cepacia lipase-catalysed preferential acylation of the secondary hydroxy group of FUdR (floxuridine) with vinyl crotonate was carried out in spite of the presence of the primary hydroxy group, and 3'-O-crotonylfloxuridine was prepared successfully for the first time. The isomerization of the double bond of crotonate, which occurs in conventional organic synthesis, could be effectively avoided during the enzymatic acylation. The effects of some key factors such as reaction medium, initial a(w) (water activity), molar ratio of vinyl crotonate to FUdR, FUdR concentration and reaction temperature on the reaction were examined. Under the optimized reaction conditions, the initial reaction rate, substrate conversion and 3'-regioselectivity of the reaction were as high as 24 mM/h, 98% and 85% respectively.
Zhao
Zhilei
Z
Laboratory of Applied Biocatalysis, South China University of Technology, 381 Wushan Road, Guangzhou, Guangdong, People's Republic of China.
Zong
Minhua
M
Li
Ning
N
D000215:Acylation; D055162:Biocatalysis; D016956:Burkholderia cepacia / Q000201:enzymology*; D055598:Chemical Phenomena; D003437:Crotonates / Q000378:metabolism*; D004800:Enzymes, Immobilized; D005467:Floxuridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008049:Lipase / Q000378:metabolism*; D012995:Solubility; D013696:Temperature; D014753:Vinyl Compounds / Q000378:metabolism; D014867:Water / Q000378:metabolism
C542577:3'-O-crotonylfloxuridine; D003437:Crotonates; D004800:Enzymes, Immobilized; D014753:Vinyl Compounds; D005467:Floxuridine; D014867:Water; D008049:Lipase