Recent advances in the synthesis of azaphenalene alkaloids: first enantioselective approaches

Abstract

Azaphenalene alkaloids are biosynthesised and segregated by diverse insects of the Coccinellidae family (ladybirds) and are believed to play an important role in the defensive mechanism against their natural predators. The particular unique framework of these alkaloids, along with their potential in the field of biological pest control, has led to several research groups developing synthetic sequences to prepare these compounds. The main purpose of the present review is to provide an update of the more recent synthetic progress towards these alkaloids, including the pioneering enantioselective approaches to chiral congeners.

(−)-Adaline from the Adalia Genus of Ladybirds Is a Potent Antagonist of Insect and Specific Mammalian Nicotinic Acetylcholine Receptors

“…Numerous other alkaloids from plants and animals have been used as therapeutic or pesticidal agents by targeting ion channels, including nAChRs [ 9 , 10 ], leading to the hypothesis that ladybird alkaloids could target nAChRs. This was confirmed when several azaphenalene alkaloids from multiple ladybird beetle species ( Figure 1 a) were found to inhibit mammalian nAChRs [ 11 ] and their enantioselective synthesis has since been described [ 12 , 13 ]. More recently, alkaloid extract from the Harlequin ladybird, Harmonia axyridis , containing 90% harmonine ( Figure 1 a), was shown to potently inhibit nAChRs from both insects and mammals [ 14 ].…”

“…It also implies that the nAChR is the natural target for the defensive chemical, a target also exploited by several classes of invertebrate pesticides [ 34 , 35 ]. We also extend the list of ladybird alkaloids that are known to target nAChRs, including the azaphenalenes from numerous species [ 11 , 12 , 13 ] and the diamine harmonine from the Harlequin ladybird, H. axyridis [ 14 ] ( Figure 1 ). (−)-adaline is structurally diverse compared to these other ladybird alkaloids having a unique carbonyl group in its structure ( Figure 1 ).…”

Nature's Chemical Weapons: Beetle Defenses

“…In particular, azaphenalenes which are tricyclic amines are responsible for the unpleasant taste. [9,10] Coccinellidae beetles seem to be a unique example of the natural occurrence of azaphenalene alkaloids. [10] The nine azaphenalene alkaloids found in ladybirds differ in their stereochemistries and the presence of a C=C bond or N-oxide.…”