Conversion of Isatins to Tryptanthrins, Heterocycles Endowed with a Myriad of Bioactivities

• Published in: European journal of organic chemistry Vol. 2019; no. 31-32; pp. 5302 - 5312
• Main Authors: Amara, Rim, Awad, Haçan, Chaker, Diana, Bentabed‐Ababsa, Ghenia, Lassagne, Frédéric, Erb, William, Chevallier, Floris, Roisnel, Thierry, Dorcet, Vincent, Fajloun, Ziad, Vidal, Joëlle, Mongin, Florence
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 01.09.2019; Wiley Subscription Services, Inc; Wiley-VCH Verlag
• Subjects: Antioxidants; Biological activity; Chemical Sciences; Chemistry; Chemistry, Organic; Chemists; Conversion; Fungicides; Heterocycles; Iodine; Isatin; Medicinal Chemistry; Organic chemistry; Physical Sciences; Potassium hydroxides; Proteasome inhibition; Science & Technology; Tryptanthrin; Tryptanthrin; Heterocycles; INDOLIC CONSTITUENTS; STEM-CELLS; ONE-POT SYNTHESIS; CATALYZED SYNTHESIS; CRYSTAL-STRUCTURE; HEPATOCYTE GROWTH-FACTOR; VISIBLE-LIGHT; Isatin; Proteasome inhibition; BIOLOGICAL EVALUATION; NONCOVALENT INHIBITION; PROTEASOME INHIBITORS; Iodine
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201900352

The numerous bioactivities exhibited by tryptanthrins led chemists to develop synthetic approaches towards this important scaffold. In particular, conversion of isatins into tryptanthrins has been the subject of several studies. In this context, by using iodine and potassium hydroxide at room temperature, we have discovered a simple way to convert isatin and seven of its 5‐substituted derivatives (Bu, F, Cl, Br, I, OMe and OCF3) into the corresponding tryptanthrins. Furthermore, a mechanism was proposed to explain this original reactivity. Finally, we evaluated the antibacterial, antifungal, antioxidant and cytotoxic properties of the synthesized tryptanthrins. The unprecedented inhibition of human 20S constitutive proteasome was finally evaluated. A straightforward and versatile synthetic approach to tryptanthrins is developed. Starting from isatins, through addition of iodine and potassium hydroxide, the method is shown to be an efficient route to these indoloquinazoline alkaloids, whose in vitro bioactivities are investigated.