Synthesis of Substituted Benzothiazepine Compounds with Medicinal Potential

作     者：Clare E. Gutteridge Brett W. Sadowski Stephen M. Hughes J. Alan Friedlander Leighton G. Rodrigo Michael C. Baxter Nathan C. Lorei Jonathan E. Harrell Michael T. O’Neil Clare E. Gutteridge;Brett W. Sadowski;Stephen M. Hughes;J. Alan Friedlander;Leighton G. Rodrigo;Michael C. Baxter;Nathan C. Lorei;Jonathan E. Harrell;Michael T. O’Neil

作者机构：Department of Chemistry United States Naval Academy Annapolis MD USA Division of Experimental Therapeutics Walter Reed Army Institute of Research Silver Spring MD USA 

出 版 物：《International Journal of Organic Chemistry》 (有机化学国际期刊（英文）)

年 卷 期：2020年第10卷第3期

页      面：123-134页

学科分类：081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学] 

主　　题：Benzothiazepine Knoevenagel Condensation Thio-Michael Addition Benzylidene Indandione 2-Aminothiophenol 

摘      要：A versatile synthetic approach toward a series of benzothiazepines with medicinal potential (for example, compound 1) that allows incorporation of structural variation at the three aromatic regions of the structure, and at the sulfur atom, was developed. Knoevenagel condensation of indan-1,3-diones with benzaldehydes, yielded 2-benzylidineindan-1,3-diones, which undewent thio-Michael addition and intramolecular imine formation upon reaction with 2-aminothiophenols, to produce the target benzothiazepines. Use of indan-1,3-diones, benzaldehydes or 2-aminothiophenols bearing further substitution enabled production of novel 5,11-dihydro-12H-benzo[b]indeno [1,2-e][1,4]thiazepin-12-one analogs 1 - 14, including compounds bearing substitution at novel positions within the scaffold.