Simple and high radiochemical yield synthesis of 2′‐Deoxy‐2′‐[¹⁸F]fluorouridine via a new nosylate precursor

Abstract

We synthesized 2'-deoxy-2'-[ 18 F]fluorouridine (7) as a radiotracer for positron emission tomography from a new nosylate precursor (6). This new precursor was synthesized from uridine in four steps. The overall synthetic yield was 9.4% and we have high stability of >98% purity up to 6 months at 48C. The optimal manual [ 18 F]fluorination conditions were 30 mg of the precursor 6 in 500 ml of acetonitrile at 1458C for 15 min with 370 MBq of [ 18 F]fluoride. The [ 18 F]fluorination yield was 76.5 AE 2.7% (n=3). After hydrolysis of protecting groups with 1 N HCl and purification by HPLC, the overall radiochemical yield and purity were 26.5 AE 1.4% and 98.2 AE 2.5%, respectively. The preparation time was 70.0 AE 10.5 min (n=3 for each result). We also developed an automated method with a radiochemical yield and purity of 24.0 AE 2.8 and 98.0 AE 1.5% (n=10) using a GE TracerLab MX chemistry module. This new nosylate precursor for 2'-deoxy-2'-[ 18 F]fluorouridine synthesis showed higher radiochemical yields and reproducibility than previous methods.Reactions were carried out for 15 min. Decay-corrected radiochemical yields from 370 MGBq/0.5 ml of [ 18 F]fluoride.

Kilogram-Scale Synthesis of 2′-C-Methyl-arabino-Uridine from Uridine via Dynamic Selective Dipivaloylation

“…We evaluated several alternative silicon protecting groups with two leaving groups, but they were either expensive or lacked the desired reactivity/selectivity for the 3′- and 5′-alcohols (Table , entries 2–5) . We also evaluated various dicarboxylic acid derivatives such as cyclic anhydrides or diacid chlorides and various acetals/ketals, and again, all of the investigated substrates exhibited reactivity/selectivity issues (Table , entries 7 and 8) . Given these collective observations, we decided to examine the simple acid chlorides more closely because of their low costs and the opportunity to control the chemoselectivity via a dynamic process.…”