Stereochemical inversion of pyrrolizidine alkaloids byMechanitis polymnia (Lepidoptera: Nymphalidae: Ithomiinae): Specificity and evolutionary significance.

Pyrrolizidine alkaloids (PAs), acquired by adults or larvae of Danainae and Ithomiinae butterflies and Arctiidae moths from plants, protect these lepidopterans against predators and are biosynthetic precursors of male sex pheromones. The investigation of PAs in many species of wild-caught adults of Ithomiinae showed lycopsamine (1) [(7R)-OH, (2'S)-OH, (3'S)-OH] as the main alkaloid. In incorporation experiments, PA-free (freshly emerged) adults of the ithomiineMechanitis polymnia were fed seven PAs: lycopsamine and four of its known natural stereoisomers-indicine (2) [(7R)-OH, (2'R)-OH, (3'S)-OH], intermedine (3) [(7R)-OH, (2'S)-OH, (3'R)-OH], rinderine (4) [(7S)-OH, (2'S)-OH, (3'R)-OH], and echinatine (5) [(7S)-OH, (2'S)-OH, (3'S)-OH], and two PAs without the 7-OH: supinine (6) [(2'S)-OH, (3'R)-OH] and amabiline (7) [(2'S)-OH, (3'S)-OH]. Males epimerized PAs 3, 4, and 5 mainly to lycopsamine (1). Females fed these same three PAs changed a smaller proportion to lycopsamine; their lesser capacity to modify PAs corresponds to their normal acquisition of already transformed PAs from males during mating rather than through visits of adults to plant sources of PAs. The alkaloids1 and2, both 7R and 3'S, were incorporated without or with minimum change by males and females. Feeding experiments with6 and7 (males only) showed an inversion at the 3' center of6 and no change in7. The inversion from 7S to 7R (probably via oxyreduction) may be closely related to the evolution of acquisition of PAs by butterflies and moths. Two hypotheses are discussed: (1) The ancestral butterflies are probably adapted to tolerate, assimilate, and use (7R)-PAs (most common in plants; all widespread 1,2-unsaturated macrocyclic PA diesters show this configuration). The development of (7R)-PA receptors in the butterflies could lead to a specialization on this configuration in two ways: to help find PA plants and to utilize these components in sexual chemical communication. A later appearance of (7S)-PAs in plants could have selected an enzymatic system for the inversion of this chiral center in order to continue producing (7R)-PA-derived pheromones. (2) The inversion would be due to the evolution of a enzyme system specialized in the transport of (7R)-PAs to the integument; the failure of this system to carry (7S)-PAs led to an enzymatic system to invert them to transportable (7R)-PAs. In this case, the 7R configuration is an effect and not a cause of (7R)-PA-derived pheromones. In both hypotheses, the partial inversion of the 3'-asymmetric center, when the butterfly was fed intermedine (3), rinderine (4), and supinine (6), could be fortuitous due to the conformation of the molecule and/or the enzymatic system.