Nepetalactones are a group of iridoid analog stereoisomers produced by Nepeta cataria (catnip) and certain other plants in the genus Nepeta in order to repel insects. They are also produced by many aphids, in which they are sex pheromones. Nepetalactones are cat attractants, and cause the behavioral effects that catnip induces in domestic cats. However, they affect visibly only about two thirds of adult cats. They produce similar behavioral effects in many other felids, especially in lions and jaguars. In 1941, the research group of Samuel M. McElvain was the first to determine the structures of nepetalactones and several related compounds.
Structure and properties
class=skin-invert-image|thumb|The relative stereochemistry of the nepetalactones
Nepetalactone has three chiral centers, two at the fusion of the two rings, and one where the methyl group attaches to the cyclopentane ring. Thus, it has eight (2) stereoisomers. The terms cis and trans are used to refer to the relative stereochemistry at the ring fusion, and also to the methyl group as compared to the lactone on the cyclopentane.
Natural occurrence
Plants belonging to the Nepeta genus produce 4 different nepetalactone stereoisomers: (cis,cis)-, (cis,trans)-, (trans,cis)- and (trans,trans)-nepetalactone. Their relative occurrence varies among plant species. Small amounts of (cis,trans)- and (trans,cis)-nepetalactone also occur in the wood of Lonicera tatarica, but its cat attractant effects are assumed to be caused by actinidine, which occurs in it in higher concentrations.
Nepetalactones are also produced by many aphids, in which they function as sex pheromones. The most common isomer in aphids is (cis,trans)-nepetalactone. Aphids also commonly produce a structurally related (1R,4aS,7S,7aR)-nepetalactol, which is also an aphid sex pheromone. Relative concentrations of these two compounds varies among aphid species.
Biosynthesis
Nepetalactone is a bicyclic monoterpene produced through the terpenoid pathway in the genus Nepeta using its starting compound geranyl pyrophosphate (GPP). There are three isomers of nepetalactone and it is suggested their stereochemistry is produced using different enzymes. Geranyl pyrophosphate undergoes hydrolysis and several oxidations to form 8-oxogeranial which can undergo a canonical activation–cyclation step in iridoid biosynthesis. Uncanonically, 8-oxogeranial will be reduced to create an 8-oxocitronellyl enol intermediate. Through a Diels–Alder reaction with a group of cyclases known as nepetalactone-related short-chain dehydrogenase enzymes (NEPS), the different stereoisomers of nepetalactone are biosynthesized. They also affect leopards (Panthera pardus). Species exhibiting overall lesser to no sensitivity include tigers (Panthera tigris), bobcats (Lynx rufus), cougars (Puma concolor) or oncillas (Leopardus tigrinus).