Meninno Sara, Volpe Chiara, Lattanzi Alessandra
Dipartimento di Chimica e Biologia "A. Zambelli", Università di Salerno, Via Giovanni Paolo II, 84084, Fisciano, Italy.
Chemistry. 2017 Apr 3;23(19):4547-4550. doi: 10.1002/chem.201700837. Epub 2017 Mar 22.
A one-pot enantioselective route to N-unprotected 2,3-dihydro-1,5-benzothiazepinones, by an organocatalyzed sulfa-Michael reaction of readily available α,β-unsaturated N-acyl pyrazoles with 2-aminothiophenols followed by silica-gel-catalyzed lactamization, has been developed. The method proceeds under mild conditions at room temperature and it requires only 1 mol % catalyst loading, to give 2-aryl/alkyl-substituted 1,5-benzothiazepines in generally good to excellent yields and enantioselectivities. The process, used for a short synthesis of antidepressant drug (R)-(-)-thiazesim, represents the first method to access enantioenriched unprotected 1,5-benzothiazepines, which are useful for rapid derivatization in drug discovery.
通过有机催化易得的α,β-不饱和N-酰基吡唑与2-氨基硫酚的硫醚-迈克尔反应，随后进行硅胶催化的内酰胺化反应，开发了一种一锅法对映选择性合成N-未保护的2,3-二氢-1,5-苯并硫氮杂䓬酮的方法。该方法在室温温和条件下进行，催化剂负载量仅需1 mol%，可得到2-芳基/烷基取代的1,5-苯并硫氮杂䓬，产率和对映选择性一般良好至优异。该方法用于抗抑郁药物(R)-(-)-噻嗪西姆的短路线合成，是获得对映体富集的未保护1,5-苯并硫氮杂䓬的第一种方法，这些化合物在药物发现中可用于快速衍生化。
