Natural Products Containing the Nitrile Functional Group and Their Biological Activities

Abstract

The importance of nitriles as a key class of chemicals with applications across the sciences is widely appreciated. The natural world is an underappreciated source of chemically diverse nitriles. With this in mind, this review describes novel nitrile-containing molecules isolated from natural sources from 1998 to 2021, as well as a discussion of the biological activity of these compounds. This study gathers 192 molecules from varied origins across the plant, animal, and microbial worlds. Their biological activity is extremely diverse, with many potential medicinal applications.

Pyrrole-2-carboxaldehydes: Origins and Physiological Activities

“…The nitrile functional group is quite interesting in the pharmaceutical standpoint of view. It is well known that other metabolites bearing nitrile group in the molecule sometimes showed strong biological activities [ 110 ]. In an investigation of the cytotoxic effects of Py-2-Cs containing 21 carbon atoms, including tri-unsaturated ( 141 ), di-unsaturated ( 144 ), mono-unsaturated ( 148 ), and non-saturated ( 109 ) compounds, the mono-unsaturated Py-2-C ( 148 ) showed the strongest activity when compared with the other compounds ( 141 , 144 , and 109 ).…”

Synthesis of cyano-substituted γ-lactams through a copper-catalyzed cascade cyclization/cyanation reaction

“…On the other hand, the cyano group, an isostere of the carbonyl group, is a versatile chemical motif and its polarity, directionality, and capacity to modulate pharmacokinetic and metabolic properties make it ubiquitous in pharmaceuticals, natural products and materials. 5 For example, anastrozole is an aromatase inhibitor used to treat estrogen-dependent breast cancer (Scheme 1). 6 Amygdalin, a natural compound found in many plant seeds, is a cyanogenic glycoside.…”

Mechanistic Investigation of the Nickel-Catalyzed Transfer Hydrocyanation of Alkynes

“…The activation of C–CN bonds has been of interest due to the abundance of nitrile groups in commodity and pharmaceutically relevant compounds and their versatility to act as suitable precursors for a plethora of other functional groups. − Initial reports showcasing the ability of low valent Ni(0) precursors − to activate nitrile groups facilitated the development of a variety of aryl cyanation reactions. − Based on these findings, further investigations towards the more challenging activation of alkyl nitriles showed that C(sp 3 )–CN bonds can be effectively activated by phosphine-supported nickel catalysts in combination with co-catalytic amounts of group 13-based Lewis acids, such as AlCl 3 . ,, This dual catalytic system was also harnessed by our group in the development of a catalytic transfer hydrocyanation reaction . In contrast, nickel-mediated alkyl nitrile activation in the absence of Lewis acids has remained scarce and is still lacking mechanistic understanding. , Pioneering work by the Jones group showcased that the C–CN bond in acetonitrile can be activated by Ni(0) precatalysts under thermal or photocatalytic conditions (Figure a); however, attempts to further extend this approach toward other alkyl nitriles remained unsuccessful. , …”