An improved method for 14C-labelling of farnesylacetic acid and its geranyl ester.
Farnesylacetic acid was efficiently labelled with 14C at the 5-position and gefarnate, a potent ulcer inhibitor, was prepared from it in radioactive form for use in metabolic studies. Condensation of [carbonyl-14C]acetyl chloride (5) with t-butyl 2-ethoxymagnesiomalonate (6) followed by acid-catalyzed deprotection and decarboxylation gave ethyl 3-oxo[3-14C]butanoate (8). Alkylation of the keto ester (8) with geranyl bromide (9) afforded the unsaturated keto ester (10), which was hydrolyzed and decarboxylated to give geranyl[2-14C]acetone (11). Grignard reaction of 11 with cyclopropylmagnesium bromide followed by treatment with hydrobromic acid yielded [4-14C]homofarnesyl bromide (13). Cyanation of 13 with potassium cyanide and subsequent hydrolysis gave [5-14C]farnesylacetic acid (1) in 6.1% yield from barium [14C]carbonate (3). Chlorination of 1 followed by esterification with geraniol afforded [5-14C]gefarnate (2) in 88% yield.
Nishioka
K
K
Takarazuka Research Center, Sumitomo Chemical Co., Ltd., Japan.
Nakatsuka
I
I
Kanamaru
H
H
D002250:Carbon Radioisotopes; D005204:Farnesol / Q000031:analogs & derivatives*; D005778:Gefarnate; D007553:Isotope Labeling / Q000379:methods*; D013729:Terpenes
D002250:Carbon Radioisotopes; D013729:Terpenes; D005778:Gefarnate; C037088:farnesylacetic acid; D005204:Farnesol