Facile synthesis of novel mutual derivatives of nucleosides and pyrimidines by regioselectively chemo-enzymatic protocol.
We established a facile regioselectively chemo-enzymatic synthesis procedure for the preparation of mutual derivatives of nucleosides and pyrimidines by sequential Markovnikov addition and acylation. Firstly, pyrimidine derivatives containing vinyl ester group were synthesized from pyrimidines and divinyl esters through Markovnikov addition catalyzed by K(2)CO(3) in DMSO at 80 degrees C, and the yields were ranged from 50% to 87%. Then regioselective acylation of ribavirin and cytarabine with pyrimidine vinyl ester was catalyzed by CAL-B (immobilized lipase from Candida antarctica) in anhydrous acetone. Reaction conditions of enzymatic acylation including enzyme resource and solvents were optimized. A series of mutual derivatives of nucleosides and pyrimidines were synthesized successfully and characterized with NMR, IR, and HRMS. This chemo-enzymatic protocol involving sequential Markovnikov addition and acylation provided a novel way of synthesizing complicated functional compounds regioselectively which was hard to be achieved either by chemical or by enzymatic methods.
Qian
Xueqi
X
Department of Chemistry, Zhejiang University, Hangzhou 310027, People's Republic of China.
Liu
Bokai
B
Wu
Qi
Q
Lv
Deshui
D
Lin
Xian-Fu
XF
D000215:Acylation; D002175:Candida / Q000201:enzymology; D002254:Carbonates / Q000737:chemistry; D002384:Catalysis; D003561:Cytarabine / Q000138:chemical synthesis / Q000737:chemistry; D004800:Enzymes, Immobilized / Q000737:chemistry*; D005656:Fungal Proteins; D008049:Lipase / Q000737:chemistry*; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D011188:Potassium / Q000737:chemistry; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry; D012254:Ribavirin / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
D002254:Carbonates; D004800:Enzymes, Immobilized; D005656:Fungal Proteins; D009705:Nucleosides; D011743:Pyrimidines; D003561:Cytarabine; D012254:Ribavirin; C037593:potassium carbonate; D008049:Lipase; C431349:lipase B, Candida antarctica; D011188:Potassium