Preparation of Tetrahydroagathic Acid:  A Serum Metabolite of Isocupressic Acid, a Cattle Abortifacient in Ponderosa Pine

Isocupressic acid (1) was used to synthetically prepare a mixture of (8S,13R,S)-labda-15,19-dioic acid (tetrahydroagathic acid) (5) via a two-step oxidation procedure followed by hydrogenation of the double bonds at C13 and C8. Reduction of the C8,17 double bond was stereospecific producing only the...

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Bibliographic Details
Published in:Journal of agricultural and food chemistry 2002-04, Vol.50 (8), p.2235-2240
Main Authors: Garrossian, Massoud, Gardner, Dale R, Panter, Kip E, James, Lynn F
Format: Article
Language:English
Subjects:
Abortifacient Agents
Abortion, Veterinary - chemically induced
Abortion, Veterinary - diagnosis
Animals
Biological and medical sciences
Carboxylic Acids - blood
Cattle
Cattle Diseases - chemically induced
Dicarboxylic Acids - blood
Dicarboxylic Acids - chemical synthesis
Diterpenes - blood
Female
Medical sciences
Oxidation-Reduction
Pinus - adverse effects
Pinus - chemistry
Plant poisons toxicology
Pregnancy
Tetrahydronaphthalenes - blood
Tetrahydronaphthalenes - chemical synthesis
Toxicology
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Summary:Isocupressic acid (1) was used to synthetically prepare a mixture of (8S,13R,S)-labda-15,19-dioic acid (tetrahydroagathic acid) (5) via a two-step oxidation procedure followed by hydrogenation of the double bonds at C13 and C8. Reduction of the C8,17 double bond was stereospecific producing only the 8S isomer and confirmed by the nOe interaction between the resulting C17 and C20 methyl groups. The 13R and 13S isomers of 5 were separated and analyzed by HPLC/MS, and (13S)-tetrahydroagathic acid was isolated and identified by comparison to a standard prepared by hydrogenation of naturally occurring (13S)-dihydroagathic acid (4). (13R,S)-dihydroagathic acid was prepared by selective sodium metal-catalyzed hydrogenation of the C13,14 allylic double bond of agathic acid (3). The prepared compounds were then used as standards to confirm the presence of 4 and 5 and their respective 13R and 13S isomers in bovine serum samples. Tetrahydroagathic acid was shown to be the only metabolite detected in serum samples taken from a suspected cattle abortion case submitted for diagnosis; and, thus, 5 could be a valuable diagnostic marker for pine needle-induced abortions. Keywords: Isocupressic acid; Pinus ponderosa; cattle abortion; diterpene acids; tetrahydroagathic acid
ISSN:0021-8561
1520-5118
DOI:10.1021/jf011501m