Biosynthetic Routes to Natural Isocyanides

Abstract

As intriguing as it may appear, natural products bearing an isocyanide function are well known in different kingdoms of living organisms. An important question in terms of biochemistry is, of course, the origin of such a functional group and the mechanisms that have evolved in biosynthetic pathways to afford the formation of isocyanides. The latest studies dedicated to such endeavours are analysed therein in view of the producing organism metabolisms (e.g. micro‐organisms, marine invertebrates). The in‐situ reactivity of natural isocyanides is also discussed as well as their biological activities.

Density Functional Theory Study into the Reaction Mechanism of Isonitrile Biosynthesis by the Nonheme Iron Enzyme ScoE

“…The biosynthesis of isonitrile groups by enzymes is unusual, but several have been reported that catalyse the reaction efficiently [37][38][39][40][41][42][43][44]. Most of those enzymes are flavindependent; however, recently, a nonheme iron dioxygenase was identified that biosynthesized an isonitrile group from R-3-((carboxymethyl)amino)butanoic acid through an oxidative decarboxylation reaction [43].…”

Antifungal mono- and dimeric nitrogenous bisabolene derivatives from a sponge in the order Bubarida from Futuna Islands

“…Instead, a methyl ketone was evidenced by a key HMBC correlation from the methyl H 3 -12 (δ H 2.28, s) to C-10 and C-11 (δ C 200.1). The large 3 J-coupling constant value of 16 Hz between H-9 and H-10 confirmed the E configuration of the double bond. In this case, no Cotton effect was observed in the ECD spectrum of 5, suggesting bubaridin E (5) to be a racemic mixture.…”

“…15 These metabolites possess a terpene scaffold bearing a nitrogen-containing functional group, the most common being isocyanide (-NC), isocyanate (-NCO), isothiocyanate (-NCS) or formamide (-NH-CHO), but also dichloroimine, carbamate, urea or amine. 16 This growing class of metabolites (over 300 to date) includes mainly sesquiterpenoids and diterpenoids that contain one or up to three nitrogenous functions around a variety of terpene skeletons. In the case of the Bubarida sponge studied here, all new compounds possess the same bisabolene skeleton characterised by a 3,6-methylalkyl disubstituted cyclohexane ring and a nitrogen always substituted at the position C-3 (mainly formamide).…”

“…18 Several biosynthetic feeding experiments with sponges maintained in aquaria have confirmed the incorporation of cyanide ions into the terpene skeleton, but the source of the cyanide is still questionned. 15,16 The main hypothesis remains that these terpenes are products of enzymatic processes by the host sponges, but microbial symbionts could be involved in the production or incorporation of the cyanide, as cyanogenesis has been well documented in bacteria. 19 Moreover, the interconversion of the precursors isocyanide-thiocyanate has been demonstrated in Axinyssa sp., 20 but their transformation to formamide or amines has not been investigated in detail.…”

Isonitriles: Versatile Handles for the Bioorthogonal Functionalization of Proteins

“…Although the isonitrile group is not found in mammals and vertebrates, the evolution of specific biosynthetic pathways has ensured their presence in many terrestrial and marine natural compounds. 4 The reactivity of isonitriles as weak nucleophiles is limited to highly electrophilic species such as resonance-stabilized carbocations, iminium, N -alkylquinolinium, and tropylium ions, which are often accompanied by a second nucleophile for a double α-addition. 5 Thus, isonitriles are mostly unreactive in the presence of biologically occurring functional groups such as alcohols, amines, thiols, carboxylic acids, aldehydes, and ketones.…”