Nishioka K, Nakatsuka I, Kanamaru H
Takarazuka Research Center, Sumitomo Chemical Co., Ltd., Japan.
Radioisotopes. 1988 Mar;37(3):133-9. doi: 10.3769/radioisotopes.37.3_133.
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.
法呢基乙酸在5位被高效地用(^{14}C)标记，强效溃疡抑制剂吉法酯以放射性形式由其制备，用于代谢研究。[羰基-(^{14}C)]乙酰氯(5)与2-乙氧基丙二酸叔丁酯(6)缩合，随后经酸催化脱保护和脱羧得到3-氧代[(3-^{14}C)]丁酸乙酯(8)。酮酯(8)与香叶基溴(9)烷基化得到不饱和酮酯(10)，其经水解和脱羧得到香叶基[(2-^{14}C)]丙酮(11)。11与环丙基溴化镁进行格氏反应，随后用氢溴酸处理得到[(4-^{14}C)]高法呢基溴(13)。13用氰化钾氰化，随后水解，以碳酸钡[(^{14}C)] (3)计，产率为6.1%得到[(5-^{14}C)]法呢基乙酸(1)。1氯化后与香叶醇酯化，产率为88%得到[(5-^{14}C)]吉法酯(2)。
