ChemInform Abstract: Nitrile-Containing Natural Products

Abstract

Naturally occurring nitriles† comprise a small and surprisingly diverse set of secondary metabolites. The structures vary from simple, long-chain alkanenitriles to architecturally complex structures such as the calyculins, with new, more complex metabolites being continually reported. The number of nitrilecontaining natural products has risen from 33, in a 1981 review,3 to more than 1204 (excluding cyanogenic glycosides) and now includes metabolites from both terrestrial and marine sources.2 The increasing number of nitrile-containing natural products highlights the need for a general classification of these compounds with this review classifying metabolites according to the hybridization of the nitrile-bearing carbon. Three general categories result; alkanenitriles, a,b-unsaturated nitriles, and aromatic nitriles. This classification emphasizes the amino acid origin of the nitriles and combines some previous sub-groups into structurally-related classes. Nitrile-containing natural products are known to be derived from amino acids in plants,5 arthropods,6 bacteria and fungi1 (Scheme 1). N-Hydroxylation and decarboxylation of amino acids afford aldoximes 3 that are enzymatically converted to the corresponding nitrile 4 through a sequence that appears to be considerably more complex than a simple dehydration.7 Cyanogenic glycosides are derived from these nitriles by a stereoselective hydroxylation–glycosylation sequence.8 Glucosinolates provide another biosynthetic route to nitrilecontaining metabolites. The biosynthesis of glucosinolates 6 is closely related to that of nitriles in proceeding through an aldoxime intermediate.9 Hydrolysis of glucosinolates affords numerous metabolites, including nitriles, where the formation of nitriles results from a complex dependence on pH, co-factors, and the nature of the substituent.10 Glucosinolate hydrolysis often occurs during cooking of Brassica crops (such as cabbage, brussel sprouts, and cauliflower) leading to increased levels of nitriles from these sources.11 2 Alkanenitriles