Highly regioselective synthesis of undecylenic acid esters of purine nucleosides catalyzed by Candida antarctica lipase B

Abstract

Regioselective undecylenoylation of purine nucleosides as potential dual prodrugs was achieved by Candida antarctica lipase B using adenosine as a model reactant. The optimum organic solvent, molar ratio of vinyl ester to nucleoside, enzyme dosage, reaction temperature and molecular sieve amount were anhydrous THF, 5:1, 20 U/ml, 45°C and 75 mg/ml, respectively. Under the optimum conditions, the initial reaction rate, yield and 5'-regioselectivity were 1.1 mM/h, 90% and >99%, respectively. The enzymatic acylation of various nucleosides furnished the desired 5'-ester derivatives with the yields of 60-95% and 5'-regioselectivities of >99%. In addition, the lipase displayed excellent operational stability in THF, and retained 96% of its initial activity after reused for five batches.

Highly Efficient and Enzymatic Regioselective Undecylenoylation of Gastrodin in 2-Methyltetrahydrofuran-Containing Systems

“…The lipase activity was was assayed with p -nitrophenyl acetate hydrolysis as a model reaction [19] . In a typical experiment, 0.6 mL phosphate buffer (50 mM, pH 8.0) containing 0.1 mL p -nitrophenyl acetate (10 mM dissolve in 2-propanol) and the enzyme was incubated at 45°C and 200 rpm for 20 min, then stopped by adding 0.1 M Na 2 CO 3 solution.…”

Novel and Highly Efficient Regioselective Route to Helicid Esters by Lipozyme TLL

“…The enzyme esterification activity was determined according to the method [14] . The specific activities of CAL-B, TLL, RML, CRL, PCL and PRL were 2.5, 0.21, 0.27, 0.68, 0.13 and 2.71 U/mg, respectively.…”

Continuous flow biocatalysis: synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus

“…[23][24][25][26] Many works had been reported on the biocatalysis of purine nucleoside esters. The lipase from C. antarctica was used to catalyze 5 0 -O-acylated adenosines by V. Gotor et al 27 In this work, the target products were obtained in DMSO for 18-24 h. Zhao et al reported that regioselective acylation of cytarabine catalyzed by Pseudomonas uorescens whole-cells was obtained aer 144 h. 28 Regioselective undecylenoylation of adenosine catalyzed by Candida antarctica lipase B needed 23 h. 29 These works are of great signicance for the biocatalysis of purine nucleoside esters. As we can see, biocatalytic method of purine nucleoside esters sometimes required long reaction times or toxic solvents.…”