Cucujolide biosynthesis in the merchant and rusty grain beetles

Most known aggregation pheromones of cucujid grain beetles are macrolides called “cucujolides”. It has recently been shown by us that cucujolide I4(E),8(E)-4,8-dimethyldecadien-10-olide] is of terpenoid origin, and that cucujolide II3(Z)-dodecen-11-olide] is of fatty acid. The objectives of this study were to determine if farnesol could serve as a precursor of cucujolide I in vivo; to study the conversion of fatty acids to cucujolide II; and to study the stereochemistry of the lactonization reactions leading to cucujolides I and II. Experiments were performed through application of stable isotope-labeling techniques, using the merchant grain beetle, Oryzaephilus mercator (Fauvel), and/or the rusty grain beetle, Cryptolestes ferrugineus (Stephens), as study insects. Exogenous (E,E)-farnesol was converted to cucujolide I. Dual-labeling studies with D and ¹⁸O indicate that this conversion proceeded with retention of the hydroxyl oxygen. Lauric and 11-hydroxydodecanoic acids were not effective precursors of cucujolide II, whereas 3(Z)-dodecenoic acid and 11-hydroxy-3(Z)-dodecenoic acid were effective precursors of cucujolide II. These data support the hypothesis that the biosynthetic route from fatty acids to cucujolide II involves chain shortening through β-oxidation to a 3(Z)-dodecenoic acid intermediate and oxidation at carbon-11 to form a 11-hydroxy-3(Z)-dodecenoic acid intermediate, followed by cylization. Dual-labeling studies with D and ¹⁸O indicate that this cyclization proceeded with retention of the C-11 hydroxyl of the 11-hydroxy-3(Z)-dodecenoic acid intermediate.