Formation of [18F]-fluorohexadecanoic acid was prohibited by rapid beta-elimination reaction

Aim: We reported the synthesis of 18F labeled α-, β- and ω-fluorhexadecanoic acid (FHA) for imaging fatty acid metabolism in the myocardium. [18F]α- and [18F]ω-FHA were successfully synthesized but [18F]β-FHA was not synthesized. We assumed that rapid β-elimination reaction prohibits the formation of [18F]β-FHA. Materials and Methods: The methyl esters of α-, β- and ω-hydroxyhexadecanoic acid were reacted with mesyl chloride in the presence of triethylamine. The mesyloxy methyl hexadecanoates were labeled with 18F by reacting with [18F]TBAF in acetonitrile at 800C for 10 min. The Radiolabeling yields were checked by Whatman No.1 chromatography. In the same reaction condition, cold fluoride (TBAF) was reacted with Ν-, β- and ω-mesyloxy methyl hexadecanoates, and the products were analyzed by GC-MS. Results: The radiolabeling yields of [18F]α- and [18F]ω-FHA were 25.5 and 45.5%, respectively. However, [18F]β-FHA was not obtained. The formation of cold form α- and ω-FHA were confirmed with molecular ion peaks (m/z = 288) by GC-MS spectrum. The β-FHA was not synthesized, but this reaction mixture had the β-elimination product of the β-mesyloxy methyl hexadecanoates, m/z - OMe group = 237, that was confirmed by GC-MS spectrum. Conclusion: In the fluoride substitution reaction of β-mesyloxy methyl hexadecanoate, we confirmed that rapid β-elimination reaction obstructs the formation of β-FHA