Controllable selective synthesis of a polymerizable prodrug of cytarabine by enzymatic and chemical methods.
Selectivity of enzymatic and chemical methods for transesterifications of cytarabine with divinyl dicarboxylates was described. Catalysis by lipase acrylic resin from Candida antarctica (CAL-B) in acetone facilitated the single step synthesis of polymerizable 5'-O-acyl cytarabine derivatives in high yields, while the use of alkaline protease from Bacillus subtilis (subtilisin) in pyridine afforded the mixture products of 5'-O-acyl and 4-N-acyl cytarabine derivatives. Interestingly, polymerizable 4-N-acyl cytarabine vinyl derivatives can be selectively prepared by chemical transesterification in dioxane. The obtained series of cytarabine derivatives would be useful for a significant monomer for a polymeric anticancer drug.
Wang
Na
N
Department of Chemistry, Zhejiang University, Hangzhou 310027, PR China.
Chen
Zhi Chun
ZC
Lu
De Shui
DS
Lin
Xian Fu
XF
D000215:Acylation; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry / Q000378:metabolism; D001412:Bacillus subtilis / Q000201:enzymology; D001426:Bacterial Proteins / Q000378:metabolism; D003561:Cytarabine / Q000737:chemistry / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D004952:Esters / Q000737:chemistry; D005656:Fungal Proteins; D008049:Lipase / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*
D000964:Antimetabolites, Antineoplastic; D001426:Bacterial Proteins; D004952:Esters; D005656:Fungal Proteins; D011108:Polymers; D011355:Prodrugs; D003561:Cytarabine; C093666:Lipozyme; D008049:Lipase; C431349:lipase B, Candida antarctica; D010450:Endopeptidases; C087822:alkaline protease