Highly regioselective acylation of 1-β-D-arabinofuranosylcytosine-catalyzed by Novozym 435 in a co-solvent mixture

ORGN 418

Xiao-feng Li, xflibio@scut.edu.cn, College of light industry and food sciences, South China University of Technology, 381 Wushan Street, Guangzhou, 510640, China, Min-Hua Zong, btmhzong@scut.edu.cn, Department of Biotechnology, South China University of Technology, 1 Wushan Street, Guangzhou, 510640, China, and Hong Wu, bbhwu@scut.edu.cn, College of Biological Sciences and Biotechnology, South China University of Technology, 1 Wushan Street, Guangzhou, 510640, China.
Novozym 435-catalyzed regioselective acylation of 1-b -D-arabinofuranosylcytosine for the preparation of its 5 ¢ - O -acyl derivative, a more powerful anti-tumor drug, has been successfully performed for the first time. The reaction was dramatically accelerated by using vinyl acetate as the acyl donor and the co-solvent mixture of pyridine and isopropyl ether (3/1, v/v) as the reaction medium. Comparative studies showed a higher Vmax, a lower Km and a lower Ea for the reaction taking place in the co-solvent mixture of pyridine and isopropyl ether (3/1, v/v) than in other media tested. The most suitable initial water activity, enzyme dosage, 1-b -D-arabinofuranosylcytosine concentration, molar ratio of vinyl acetate to 1-b -D-arabinofuranosylcytosine and reaction temperature were 0.11, 30 U/ml, 40 mM, 15:1 and 50°C, respectively, under which the substrate conversion and the regioselectivity were as high as > 97 % and >99%, respectively after a reaction time of 12 h.
 

Bioorganic, Metal-Mediated Reactions, and Molecular Recognition
8:00 PM-10:00 PM, Tuesday, 30 August 2005 Washington DC Convention Center -- Hall A, Poster

Division of Organic Chemistry

The 230th ACS National Meeting, in Washington, DC, Aug 28-Sept 1, 2005