Efficient synthesis of 5'-O-laurate of 1-beta-D-arabinofuranosylcytosine via highly regioselective enzymatic acylation in binary solvent mixtures

Xiao-feng Li; Min-hua Zong; Guang-lei Zhao

doi:10.1016/j.bmcl.2010.05.077

Efficient synthesis of 5'-O-laurate of 1-beta-D-arabinofuranosylcytosine via highly regioselective enzymatic acylation in binary solvent mixtures

Bioorg Med Chem Lett. 2010 Jul 15;20(14):4125-7. doi: 10.1016/j.bmcl.2010.05.077. Epub 2010 Jun 10.

Authors

Xiao-feng Li¹, Min-hua Zong, Guang-lei Zhao

Affiliation

¹ State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, Wushan Road 381, Guangzhou 510641, China.

PMID: 20541403
DOI: 10.1016/j.bmcl.2010.05.077

Abstract

Regioselective enzymatic acylations of 1-beta-D-arabinofuranosylcytosine (ara-C) with vinyl laurate (VL) in binary organic solvents were explored for the preparation of 5'-O-laurate of ara-C. Among the nine kinds of enzymes, Novozym 435 showed the highest regioselectivity (>99.9%) towards the 5'-OH of ara-C. This lipase showed higher catalytic activity in hexane-pyridine than in other tested solvent mixtures. The most suitable VL to ara-C molar ratio, initial water activity, and reaction temperature were shown to be 15:1, 0.07, and 50 degrees C, respectively, under which the initial reaction rate and the maximum substrate conversion were as high as 84.0 mmol L(-1) h(-1) and 98.1%, respectively. The product of Novozym 435-catalyzed acylation was characterized by (13)C NMR and confirmed to be 5'-O-laurate of ara-C.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acylation
Catalysis
Cytarabine / chemical synthesis*
Cytarabine / chemistry
Enzymes / chemistry*
Solvents / chemistry*
Stereoisomerism

Substances

Enzymes
Solvents
Cytarabine