5'-衍生化核苷在振动球磨机中的亲核取代反应

Eguaogie Olga, Conlon Patrick F, Ravalico Francesco, Sweet Jamie S T, Elder Thomas B, Conway Louis P, Lennon Marc E, Hodgson David R W, Vyle Joseph S

School of Chemistry and Chemical Engineering, Queen's University Belfast, David Keir Building, Stranmillis Road, Belfast BT9 5AG, UK.

Durham University, Department of Chemistry, Lower Mountjoy, Stockton Road, Durham DH1 3LE, UK.

Beilstein J Org Chem. 2017 Jan 13;13:87-92. doi: 10.3762/bjoc.13.11. eCollection 2017.

Vibration ball-milling in a zirconia-lined vessel afforded clean and quantitative nucleophilic displacement reactions between 4-methoxybenzylthiolate salts and nucleoside 5'-halides or 5'-tosylates in five to 60 minutes. Under these conditions, commonly-encountered nucleoside cyclisation byproducts (especially of purine nucleosides) were not observed. Liquid-assisted grinding of the same 5'-iodide and 5'-tosylate substrates with potassium selenocyanate in the presence of DMF produced the corresponding 5'-selenocyanates in variable yields over the course of between one and eleven hours thereby avoiding the preparation and use of hygroscopic tetrabutylammonium salts.

在氧化锆衬里的容器中进行振动球磨，可使4-甲氧基苄硫醇盐与核苷5'-卤化物或5'-甲苯磺酸盐之间在5至60分钟内发生干净且定量的亲核取代反应。在这些条件下，未观察到常见的核苷环化副产物（尤其是嘌呤核苷的副产物）。在DMF存在下，将相同的5'-碘化物和5'-甲苯磺酸盐底物与硒氰酸钾进行液体辅助研磨，在1至11小时的过程中以不同产率生成相应的5'-硒氰酸盐，从而避免了制备和使用吸湿性的四丁基铵盐。