Heterocyclic rings composed of sulfur, e.g., benzothiazepine, and benzothiazines are well known for their widespread biological role and medicinal activities. Benzothiazepine structure is so multifunctional that a great number of known drugs such as dithiazem, clentiazem, and thiazesim possess such structure. Benzothiazines also demonstrate widespread medicinal properties such as antimicrobial, antimalarial. New developments in the methodology of biocatalysts, utilizing hydrolases, has provided new horizons in organic and medicinal synthesis. Given the potential for the multicomponent syntheses in industry and medicinal chemistry, there is no better strategy than utilizing enzyme-catalyzed synthesis. The lipase separated from the fungus Aspergillus niger (ANL) has been widely utilized as catalyst and is known as GRAS (Generally Regarded as Safe enzymes) by FDA. In continuation of our general interest in the synthesis of heterocyclic compounds through MCRs in the presence of nanocatalysts 5, The retrievable nanostructure catalyst (Fe3O4 NPs@lipase) that we synthesized in previous work, was asserted to be an efficient heterogeneous catalyst in the synthesis of benzothiazepine derivatives through three-component reaction of coumarine-3-carboxylic acid derivatives, 2-aminothiophenol, and alkyl isocyanides at room temperature under mild conditions. The structure of the novel derivatives products was confirmed by FT-IR, 1H and 13C NMR spectroscopy and Mass spectrometry.
