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 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.
Garrossian
Massoud
M
Poisonous Plant Research Laboratory, Agricultural Research Service, U. S. Department of Agriculture, 1150 East 1400 North, Logan, Utah 84341, USA.
Gardner
Dale R
DR
Panter
Kip E
KE
James
Lynn F
LF
D000019:Abortifacient Agents; D000034:Abortion, Veterinary / Q000139:chemically induced / Q000175:diagnosis; D000818:Animals; D002264:Carboxylic Acids / Q000097:blood*; D002417:Cattle; D002418:Cattle Diseases / Q000139:chemically induced; D003998:Dicarboxylic Acids / Q000097:blood* / Q000138:chemical synthesis*; D004224:Diterpenes / Q000097:blood*; D005260:Female; D010084:Oxidation-Reduction; D028223:Pinus / Q000009:adverse effects* / Q000737:chemistry*; D011247:Pregnancy; D013764:Tetrahydronaphthalenes / Q000097:blood* / Q000138:chemical synthesis*
D000019:Abortifacient Agents; D002264:Carboxylic Acids; D003998:Dicarboxylic Acids; D004224:Diterpenes; D013764:Tetrahydronaphthalenes; C110793:isocupressic acid; C110795:agathic acid