Synthesis of pyrrol-[1,2-a]indole-1,8(5H)-diones as new synthones for developing novel tryciclic compounds of pharmaceutical interest

Abstract

In the course of our work aimed at developing novel heterocycles of pharmaceutical interest, a new tricycle, the tetrahydropyrrolo[1,2-a]indole-1,8-dione, has been synthesized by an intramolecular Friedel-Crafts acylation, as a synthon suitable to be functionalized to give novel compounds with potential biological properties. Also, an unusual nucleophilic α-addition to methyl propiolate by 1,5,6,7-tetrahydro-4H-indol-4-one was observed and discussed.

4,5,6,7-Tetrahydroindol-4-Ones as a Valuable Starting Point for the Synthesis of Polyheterocyclic Structures

“…Electrophilic aromatic substitution (EAS) onto pyrroles readily occurs at the C-2 position. Sechi et al N -alkylated pyrrole 1 with acrylonitrile to obtain 28 followed by basic hydrolysis to 9 and polyphosphoric acid (PPA) mediated intramolecular Friedel-Crafts acylation to afford polyheterocyclic structure 30 in an overall yield of 45% ( Scheme 2 Route A) [ 36 ]. Interestingly, Wolff-Kishner reduction of 30 in diethylene glycol (DEG) was selective for one ketone functionality, leading to 31 in 22% yield.…”

Chemical Reactivity and Skin Sensitization Studies on a Series of Chloro- and Fluoropyrroles—A Computational Approach

“…Pyrrole derivatives are nitrogen-containing heterocyclic compounds with a five-membered ring that are extensively found in a variety of natural and synthetic chemicals with useful bioactivities. Pyrrole derivatives have been used in a variety of applications, pharmaceutics, − antibacterial, − antiviral, , anti-inflammatory, − analgesic, anticancer, , antihyperlipidemic, and antihyperglycemic medicines, , in addition to their biological action.…”

Synthesis and Evaluation of Novel Pyrroles and Pyrrolopyrimidines as Anti-Hyperglycemic Agents

“…For several decades, interest in pyrrole derivatives increases due to their pharmaceutical importance [ 1 – 3 ], such as antimicrobial [ 4 – 8 ], antiviral [ 9 , 10 ], anti-inflammatory [ 11 – 13 ], analgesic [ 14 ], antitumor [ 15 , 16 ], antihyperlipidemic [ 17 ], anticonvulsant [ 18 ], and antihyperglycemic agents [ 19 , 20 ], as shown in Figures 1 and 2(a) .…”