Use of fluorous and solid-phase electrophiles as scavengers for excess amine in the preparation of sulfur-35 labelled radioligands

Abstract

SummaryA method for scavenging excess amines in sulfur-35-labeled radioligand preparations using fluorous scavengers has been developed in an effort to simplify the purification. This fluorous scavenging has been shown to be effective at removing excess amines from several [35 S]sulfonylation mixtures. In many cases this results in one less semipreparative HPLC purification, and thus in higher radiochemical yield and time savings. Fluorous scavenging was compared to the use of a solid-phase resin (PSisocyanate) and determined to be approximately equal with respect to recovery of radioactive product. However, the fluorous scavengers were shown to be more effective than solid-phase resin for removing basic amine components.

Use of perfluoro groups in nucleophilic 18F‐fluorination

“…Compounds 7 and 9 (Scheme 6) were prepared using the published procedure. 6 1,1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8-Heptadecafluoro-10-iododecane was converted to (diaminomethylene) (3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl)sulfonium iodide (23) by reaction with thiourea in ethanol. This was further transformed into the sulfonyl chloride 24 and combined with phenylmethanol or 4-phenylbutan-1-ol to give the respective compound 7 or 9.…”

“…8 F-SPE was used in combination with fluorous scavengers in a 35 S-labelling. 9 Fluorous separation techniques are methods for separating fluorous or fluorous-labelled molecules from other types of molecules, or from each other, based primarily on the structure of their fluorous domain(s). 4 These techniques are based on the interaction between a fluorous medium and a fluorous portion of a molecule, and include liquid-liquid extraction with organic and fluorous solvents, 10 F-SPE and fluorous HPLC.…”

“…The residue was purified by column chromatography (CH 2 Cl 2 ) to yield 6 as yellow crystals (0.350 g, 10%). (Diaminomethylene) (3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl)sulfonium iodide (1.184 g, 1.82 mmol) was dissolved in a mixture of 10 mL acetic acid and 2 mL H 2 O, then cooled to 101C. In another flask, which was cooled to 01C, HCl (9.6 mL) was added dropwise to KMnO 4 (3.635 g, 23.0 mmol) to give Cl 2 (g).…”

A hybrid solid‐fluorous phase radioiodination and purification platform

“…To eliminate the need for HPLC, alternative labeling and purification methods employing solid‐phase synthesis and solid‐phase extraction (SPE) have been developed for a variety of medical isotopes. These include systems based on polymer‐supported precursors and fluorous‐tagged molecules . In solid‐phase labeling, compounds are linked to insoluble supports via covalent bonds or ionic interactions in a way that the desired product is released upon labeling and isolated by simple filtration.…”

“…In solid‐phase labeling, compounds are linked to insoluble supports via covalent bonds or ionic interactions in a way that the desired product is released upon labeling and isolated by simple filtration. For the fluorous labeling strategy (FLS), fluorous‐tagged precursors, which are prepared and purified using traditional synthetic methods, are converted to nonfluorous analogues upon labeling. The fluorous precursor is separated from the desired radiolabeled compound by passing the reaction mixture through a fluorous SPE (FSPE) cartridge …”