Di Carmine Graziano, Ragno Daniele, De Risi Carmela, Bortolini Olga, Giovannini Pier Paolo, Fantin Giancarlo, Massi Alessandro
Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Ferrara, Via Luigi Borsari, 46, I-44121 Ferrara, Italy.
Org Biomol Chem. 2017 Oct 25;15(41):8788-8801. doi: 10.1039/c7ob02259j.
A strategy for the synthesis of biologically relevant 5-hydroxy-imidazolidine-2-thione derivatives is presented. A novel class of α-sulfonylamines have been suitably prepared (46-81% yield) as precursors of formal benzylidenethiourea acceptors; these are generated in situ and intercepted by N-heterocyclic carbene (NHC)-activated aldehydes affording open-chain aza-benzoin-type adducts, which in turn undergo an intramolecular aza-acetalization reaction in a one-pot fashion. A thiazolium salt/triethylamine couple proved to be the more effective system to trigger the domino sequence giving the target heterocycles in good yields (45-97%) and diastereoselectivities (up to 99 : 1 dr). The multigram scale synthesis and elaboration of a selected 5-hydroxy-imidazolidine-2-thione compound is also described.
本文提出了一种合成具有生物学相关性的5-羟基咪唑烷-2-硫酮衍生物的策略。一类新型的α-磺酰胺已被适当地制备出来（产率为46-81%），作为甲醛苄叉硫脲受体的前体；这些前体在原位生成，并被N-杂环卡宾（NHC）活化的醛捕获，得到开链氮杂苯偶姻型加合物，这些加合物进而以一锅法进行分子内氮杂缩醛化反应。事实证明，噻唑鎓盐/三乙胺组合是引发多米诺序列的更有效体系，能以良好的产率（45-97%）和非对映选择性（高达99:1 dr）得到目标杂环化合物。本文还描述了一种选定的5-羟基咪唑烷-2-硫酮化合物的多克规模合成及精制过程。
