3′-Sulfonylesters of 2,5′-anhydro-1-(2-deoxy-β-d-threo-pentofuranosyl)thymine as precursors for the synthesis of [¹⁸F]FLT: syntheses and radiofluorination trials

Abstract 

Title compounds [3′-sulfonylesters of 2,5′-anhydro-1-(2-deoxy-β-d-threo-pentofuranosyl)thymine: 2,5′-anhydro-1-(2-deoxy-3-methanesulfonyl-β-d-threo-pentofuranosyl)thymine (1a); 2,5′-anhydro-1-(2-deoxy-3-(4-nitrobenzenesulfonyl)-β-d-threo-pentofuranosyl)thymine (1b); 2,5′-anhydro-1(-2-deoxy-3-(toluenesulfonyl)-β-d-threo-pentofuranosyl)thymine (1c); and 2,5′-anhydro-1(-2-deoxy-3-(2,2,2-trifluoroethanesulfonyl)-β-d-threo-pentofuranosyl)thymine 1d] were synthesized, and their use as starting materials for the synthesis of 3′-deoxy-3′-[¹⁸F]fluorothymidine ([¹⁸F]FLT) was investigated. Radiofluorination of Compound 1b and subsequent hydrolysis with NaOH, in solution or on solid support, yielded a product with the same retention on radio thin-layer chromatography as [¹⁸F]FLT. However, careful analysis with high-performance liquid chromatography could not identify the product to be [¹⁸F]FLT. From several options that were investigated to identify the obtained product, it was shown that fluorination had occurred at the nitro group of the nosylate, and not at the 3′-position. Other sulfonate esters (Compounds 1a, 1c and 1d) did not give any fluorination under any of the investigated reaction conditions. It had to be concluded that title compounds are not suitable as starting materials for the synthesis of [¹⁸F]FLT under the described conditions.

Keywords: 3′-Sulfonylesters, 2,5′-Anhydro-1-(2-deoxy-β-d-threo-pentofuranosyl)thymine, [¹⁸F]FLT, Radioflurination