PSIM催化核苷类化合物3'-酯选择性合成中的底物识别

Substrate Recognition of the PS IM in Regioselective Synthesis of Nucleoside Analogs 3'-O-Esters

研究了有机溶剂中酶促核苷类化合物3'-酯高区域选择性的合成反应,探讨了核苷结构中R1位取代基变化对酶促酰化反应的影响.结果表明:来源于Burkholderia cepacia的固定化脂肪酶PS IM在有机溶剂THF中的催化效果最佳,且酰化反应的优势位点均为3'-羟基(90%～>99%);随着核苷中R1位取代基由F变化至CF3或酰基供体链长由C6增加至C14,该酰化反应的3'-区域选择性均呈现逐渐增加的趋势,构效关系分析表明,这主要源于PS IM酶特殊的活性中心结构.

Regioselective enzymatic acylations of nucleosides with vinyl esters in organic solvents were studied for the preparation of T-O-esters of the nucleosides. The influence of R1 substituent in the nucleosides on T-OH regioselective acylation catalyzed by Burkholderia cepacia liapse was investigated. The results revealed that the immobilized lipase of PS IM from Burkholderia cepacia showed the highest regioselectivity towards the 3＇-OH of nucleosides （90%- 〉99%） among the lipases tested. Moreover, the 3＇-regioselectivity enhanced not only with the increment of the aliphatic chain of the acyl donors （C6, C10 and C14）, but also with the increasing hydrophobicity of R1 group of 2＇-deoxynucleosides. These observations were mainly attributed to the specific structure feature of the PS IM.