Synthesis and Antimicrobial Activity of Some Pyrrolo[1,2,3-de]-1,4-benzothiazines, Part 2

Abstract

Acid catalyzed cyclization reactions of both 3‐alkyl‐ and 3‐aryl‐substituted N‐/2,2‐dialkoxyethyl)‐3,4‐dihydro‐2H‐1,4‐benzothiazines (2) lead to 2,3‐dihydro‐pyrrolo[1,2,3‐de]‐1,4‐benzothiazines (3). The pyrrolobenzothiazine structure was deduced on the basis of 2D 1H NMR‐NOESY experiments and fully determined by X‐ray data. Compounds 3a‐c showed poor antibacterial activity. However, the 3‐phenyl‐N‐(2,2‐dimethoxyethyl)‐3,4‐dihydro‐2H‐1,4‐benzothiazine (2b′) showed antifungal activity against Aspergillus niger 16‐fold greater than miconazole.

Diethyl 1-benzyl-2,2-dioxo-4-phenyl-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[2,1-c][1,4]thiazine-1,3-dicarboxylate

“…For the biological and pharmacological properties of compounds containing the pyrrolidine sub-structure, see: Hemming & Patel (2004); Kueh et al (2003). For biological properties of compounds containing the pyrrolothiazine scaffold, see: Armenise et al (1991Armenise et al ( , 1998. For ring puckering analysis, see: Cremer & Pople (1975).…”

“…Compounds containing the pyrrolothiazine scaffold have also been shown to exhibit anti-inflammatory, anti-fungal and anti-microbial activities (Armenise et al, 1998;Armenise et al, 1991).…”

Functionalized 1,4‐Benzothiazine: A Versatile Scaffold with Diverse Biological Properties

“…Over the years, 4 H ‐1,4‐benzothiazines have constituted an important class of heterocycles which, even when part of a complex molecule 1, possess a wide spectrum of biological activities 2–4. Due to the presence of a fold along the nitrogen sulfur axis, the biological activity of some 1,4‐benzothiazines is similar to that of phenothiazines, featuring the same structural specificity 5–10.…”

Synthesis and docking studies of thiophene scaffolds in COX-2

“…4 Some imidazo [2,1-b]- [1,3]thiazines and pyrimido [2,1-b]- [1,3]thiazines are well known antiinflammatory agents. 5,6 Likewise, thiophene compounds are well known to exhibit various biological and medicinal activities such as BACE1 inhibitors, 7 antitubercular, 8 anti-depressant, 9 anti-inflammatory, 10 anti-HIV PR inhibitors, 11 and anti-breast cancer activities.…”