Promiscuous Zinc-Dependent Acylase-Mediated One-Pot Synthesis of Monosaccharide-Containing Pyrimidine Derivatives in Organic Medium

作者：Wu, Qi; Xu, Jian-Ming; Xia, Li; Wang, Jun-Liang; Lin, Xian-Fu^*

来源：Advanced Synthesis & Catalysis, 2009, 351(11-12): 1833-1841.

DOI：10.1002/adsc.200900161

• aminoacylase
• catalytic promiscuity
• enzyme catalysis
• Michael addition
• one-pot synthesis
• pyrimidine derivatives

A facile one-pot synthesis route to monosaccharide-containing pyrimidine derivatives was developed by combining the two types of catalytic activities of one enzyme in an organic medium, i.e., the Michael addition/acylation activities of zinc-dependent D-aminoacylase (DA) from Escherichia coli. First, the stepwise approach was investigated. DA showed higher activity towards the Michael addition than acylation in this reaction system. The enzymatic Michael additions of pyrimidines to vinyl acrylate proceeded very rapidly and the initial reaction rates for the Michael addition of pyrimidines to vinyl acrylate were 7.2-1.6.5 mM min(-1). The catalytic specificity of aminoacylases toward Michael addition was demonstrated by the combination of different control experiments. Then, the two steps could be performed in one pot and a single aminoacylase catalyzed one-pot biotransformation was constructed. Using this strategy, a series of saccharide-pyrimidine complexes with potentially biological and pharmacological applications was prepared efficiently. This high Michael addition activity of zinc-dependent aminoacylases and the novel single aminoacylase-catalyzed one-pot synthesis combining two catalytic activities in vitro is of practical significance in expanding the application of enzymes and in the evolution of new biocatalysts.

• 出版日期2009-8
• 单位浙江大学