Medicinal Chemistry of Isocyanides

Abstract

In eons of evolution, isocyanides carved out a niche in the ecological systems probably thanks to their metal coordinating properties. In 1859 the first isocyanide was synthesized by humans and in 1950 the first natural isocyanide was discovered. Now, at the beginning of XXI century, hundreds of isocyanides have been isolated both in prokaryotes and eukaryotes and thousands have been synthesized in the laboratory. For some of them their ecological role is known, and their potent biological activity as antibacterial, antifungal, antimalarial, antifouling, and antitumoral compounds has been described. Notwithstanding, the isocyanides have not gained a good reputation among medicinal chemists who have erroneously considered them either too reactive or metabolically unstable, and this has restricted their main use to technical applications as ligands in coordination chemistry. The aim of this review is therefore to show the richness in biological activity of the isocyanidecontaining molecules, to support the idea of using the isocyanide functional group as an unconventional pharmacophore especially useful as a metal coordinating warhead. The unhidden hope is to convince the skeptical medicinal chemists of the isocyanide potential in many areas of drug discovery and considering them in the design of future drugs.

Experimental Treatment of Hazardous Ash Waste by Microbial Consortium Aspergillus niger and Chlorella sp.: Decrease of the Ni Content and Identification of Adsorption Sites by Fourier-Transform Infrared Spectroscopy

“…However, this peak may also be associated with the amides bound in proteins ( Forfang et al, 2017 ) or chitin ( Rinaudo, 2006 ), as stretching vibrations of the N–H group and associated absorption around 3280 cm –1 are characteristic for both of these components. The peak with a maximum at 2143 cm –1 in the A. niger spectrum can be associated with isocyanides, which have been identified in various microorganisms, including Aspergillus species ( Massarotti et al, 2021 ). According to Bittante and Cecchinato (2013) , isocyanides show characteristic absorption between 2110 and 2165 cm –1 .…”

The Dark Side of Isocyanides: Visible-Light Photocatalytic Activity in the Oxidative Functionalization of C(sp3)–H Bonds

“…As a whole, the experimental data provided evidence of the potential exploitation of aromatic isocyanides as a new class of highly tunable organic photocatalysts. Worth of note, isocyanides are nowadays considered a class of widely accessible compounds, with thousands of derivatives endowed with no or limited toxicity reported in the literature and readily synthesizable from the corresponding amines. , Actually, the addition of electron-withdrawing or electron-donor groups on their aromatic moiety, as well as the ring expansion to polycyclic scaffolds, could lead to easily accessible and fine modulation of their redox and optical properties, which could expand the substrate scope to a broader range of C­(sp 3 )–H bonds. Such investigations are currently in progress in our laboratories.…”

Transition‐Metal‐Catalyzed Cross‐Coupling and Sequential Reactions of Azides with Isocyanides

“…By detailed experimental and theoretical studies, authors observed that the nitrene transfer to isocyanide was a concerted and turnover‐limiting step of the overall route. Interestingly, the previously putative metalla−aziridine intermediate [5b] was not involved during this Pd‐catalyzed cross‐coupling process.…”