In vitro biotransformations of isocupressic acid by cow rumen preparations: formation of agathic and dihydroagathic acids.

摘要

Isocupressic acid (15-hydroxylabda-8(17),13E-dien-19-oic acid), a causative agent of abortion in cows, incubated under anaerobic conditions for 48 h in an in vitro ruminal fluid mixture, was transformed into 2 metabolites, identified as agathic acid(labda-8(17),13(E)-diene-15,19-dioic acid) and dihydroagathic acid (labda-8(17)-ene-15,19-dioic acid). Identities were confirmed by chemical conversions of isocupressic acid and imbricataloic acid. Structures of synthetic metabolites were confirmed by 1H and 13C NMR, specific rotation, GC-MS and high-resolution MS. Plasma obtained from cows that were fed Pinus ponderosa (Ponderosa pine) needles contained (13R,S)-dihydroagathic acid but not isocupressic acid or agathic acid. It was suggested that isocupressic acid is metabolically oxidized to agathic acid, subsequently reduced to (13R,S)-dihydroagathic acid in the rumen, and then absorbed into the bloodstream of cattle.