Biosynthesis of scarab beetle pheromones - Enantioselective 8-hydroxylation of fatty acids

Chemical communication in scarab beetles (Coleoptera: Scarabaeidae) is achi eved with a wide variety of pheromones, but one typical structure is the ga mma-lactone having a long unsaturated hydrocarbon chain. Several species ut ilize (R,Z)-5-(-)-(oct-1-enyl)-oxacyclopentan-2-one (buibuilactone), (R,Z)- 5-(-)-(dec-1-enyl)-oxacyclopentan-2-one and (S,Z)-5-(+)-(dec-1-enyl)-oxacyc lopentan-2-one [(R)-japonilure and (S)-japonilure]. Using deuterated precur sors, we have demonstrated that these compounds are biosynthesized from fat ty acids. (9,10-d(4))-Palmitic acid, (9,10-d(4))-stearic acid, (9,10-d(2))- palmitoleic acid, (9,10-d(2))-oleic acid, (9,10-d(2))-8-hydroxypalmitoleic acid and (9,10-d(2))-8-hydroxyoleic acid were readily incorporated by femal e Anomala cuprea into the pheromone molecules, while (Z)-(5,6-d(2))-5-dodec enoic acid and (Z)-(5,6-d(2))-5-tetradecenoic acid were not. Therefore, the reaction pathway starts from saturated fatty acids, involves their desatur ation, followed by 8-hydroxylation, chain shortening and cyclization. The p roducts obtained from racemic (9,10-d(2))-8-hydroxypalmitoleic acid and (9, 10-d(2))-8-hydroxyoleic acid were also racemic, implying that the steps fol lowing hydroxylation were not stereospecific. Perdeuterated palmitic acid w as applied to disclose the mechanism of the unique hydroxylation reaction. Retention of all deuterium atoms implied that this reaction was a direct pr ocess mediated by a specific fatty acid hydroxylase, and preceding desatura tion or epoxidation was not involved.