TITLE:
Synthesis of Substituted Benzothiazepine Compounds with Medicinal Potential
AUTHORS:
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
KEYWORDS:
Benzothiazepine, Knoevenagel Condensation, Thio-Michael Addition, Benzylidene Indandione, 2-Aminothiophenol
JOURNAL NAME:
International Journal of Organic Chemistry,
Vol.10 No.3,
September
21,
2020
ABSTRACT: 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.