A fascinating example is provided by the pupae of the coccinellid beetle, Epilachna borealis, which exert a chemical defensive mechanism against predators through the secretion from their glandular hairs of droplets containing a library of hundreds of large-ring (up to 98 members) macrocyclic polyamines, with the simplest example having the generic formula shown (8; Scheme 2).17 The use of three simple (2-hydroxyethyl amino)alkanoic acid precursors in the building of these libraries provides clear evidence that combinatorial chemistry was pioneered and widely used in Nature for the synthesis of biologically active compound libraries.