Dai Qing, Frederiksen John K, Anderson Vernon E, Harris Michael E, Piccirilli Joseph A
Department of Biochemistry & Molecular Biology, Department of Chemistry, and Howard Hughes Medical Institute, The University of Chicago, MC 1028, Chicago, Illinois 60637, USA.
J Org Chem. 2008 Jan 4;73(1):309-11. doi: 10.1021/jo701727h. Epub 2007 Dec 4.
Lack of sufficient quantities of isotopically labeled materials has precluded the use of heavy atom isotope effects to investigate mechanisms of nucleotidyl transfer reactions in nucleic acids. Here we achieve regioselective opening of 2,2'-cyclouridine with [(18)O2]benzoic acid/potassium hydride, allowing an efficient "one-pot" synthesis of [2'-18O]uridine in 88% yield. Conversion to the corresponding phosphoramidite enables solid-phase synthesis of [2'-(18)O] RNA substrates for isotope effect studies with nucleotidyl transferases and hydrolases.
缺乏足够数量的同位素标记材料使得无法利用重原子同位素效应来研究核酸中核苷酸转移反应的机制。在此，我们利用[(18)O2]苯甲酸/氢化钾实现了2,2'-环尿苷的区域选择性开环，从而以88%的产率高效“一锅法”合成了[2'-18O]尿苷。将其转化为相应的亚磷酰胺可实现[2'-(18)O]RNA底物的固相合成，用于核苷酸转移酶和水解酶的同位素效应研究。
