Aminodifluorosulfinium Tetrafluoroborate Salts as Stable and Crystalline Deoxofluorinating Reagents

Beaulieu, Françis; Beauregard, Louis-Philippe; Courchesne, Gabriel; Couturier, Michel; LaFlamme, François; L’Heureux, Alexandre

doi:10.1021/ol902039q

Cited by 194 publications

(74 citation statements)

References 23 publications

(28 reference statements)

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“…A standard of FPOIBG was synthesized as shown in Scheme 2. Iodo-cresol 1a was treated with 3-bromo-1-propanol to obtain alcohol 7 in 93% yield, which was subjected to deoxofluorination using an aminodisulfuorosulfinium tetrafluoroborate salt [34] to obtain the fluoro derivative 8 in 71% yield. The sequence of benzylic bromination (45%), guanidinylation (10%), and removal of Boc groups yielded the final product (74%).…”

Section: Resultsmentioning

confidence: 99%

“…A mixture of 7 (3.5 g; 11.98 mmol), triethylamine trihydrofluoride (2.90 g; 17.97 mmol), and XtalFluor-E ® /(diethylamino)difluorosulfonium tetrafluoroborate [34] (4.12 g, 17.97 mmol) in 50 mL of acetonitrile was stirred under argon at 20°C overnight. Acetonitrile was evaporated, and the residual material was partitioned between ethyl acetate and water.…”

Section: Methodsmentioning

confidence: 99%

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Synthesis and evaluation of 4-[18F]fluoropropoxy-3-iodobenzylguanidine ([18F]FPOIBG): A novel 18F-labeled analogue of MIBG

Vaidyanathan

McDougald

Koumarianou

et al. 2015

Nuclear Medicine and Biology

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Introduction Radioiodinated meta-iodobenzylguanidine (MIBG), a norepinephrine transporter (NET) substrate, has been extensively used as an imaging agent to study the pathophysiology of the heart and for the diagnosis and treatment of neuroendocrine tumors. The goal of this study was to develop an 18F-labeled analogue of MIBG that like MIBG itself could be synthesized in a single radiochemical step. Towards this end, we designed 4-fluoropropoxy-3-iodobenzylguanidine (FPOIBG). Methods Standards of FPOIBG and 4-fluoropropoxy-3-bromobenzylguanidine (FPOBBG) as well as their tosylate precursors for labeling with 18F, and a tin precursor for the preparation of radioiodinated FPOIBG were synthesized. Radiolabeled derivatives were synthesized by nucleophilic substitution and electrophilic iododestannylation from the corresponding precursors. Labeled compounds were evaluated for NET transporter recognition in in vitro assays using three NET-expressing cell lines and in biodistribution experiments in normal mice, with all studies performed in a paired-label format. Competitive inhibition of [125I]MIBG uptake by unlabeled benzylguanidine compounds was performed in UVW-NAT cell line to determine IC50 values. Results [18F]FPOIBG was synthesized from the corresponding tosylate precursor in 5.2 ± 0.5% (n = 6) overall radiochemical yields starting with aqueous fluoride in about 105 min. In a paired-label in vitro assay, the uptake of [18F]FPOIBG at 2 h was 10.2 ± 1.5%, 39.6 ± 13.4%, and 13.3 ± 2.5%, in NET-expressing SK-N-SH, UVW-NAT, and SK-N-BE(2c) cells, respectively, while these values for [125I]MIBG were 57.3 ± 8.1%, 82.7 ± 8.9%, and 66.3 ± 3.6%. The specificity of uptake of both tracers was demonstrated by blocking with desipramine. The 125I-labeled congener of FPOIBG gave similar results. On the other hand, [18F]FPOBBG, a compound recently reported in the literature, demonstrated much higher uptake, albeit less than that of co-incubated [125I]MIBG. IC50 values for FPOIBG were higher than that obtained for MIBG and FPOBBG. Unlike the case with [18F]FPOBBG, the heart uptake [18F]FPOIBG in normal mice was significantly lower than that of MIBG. Conclusion Although [18F]FPOIBG does not appear to warrant further consideration as an 18F-labeled MIBG analogue, analogues wherein the iodine in it is replaced with a chlorine, fluorine or hydrogen might be worth pursuing. Advances in knowledge and implications for patient care An 18F-labeled analogue of the well-known radiopharmaceutical MIBG could have significant impact, potentially improving imaging of NET related disease in cardiology and in the imaging of neuroendocrine tumors. Although 18F-labeled analogues of MIBG have been reported including LMI1195, we undertook this work hypothesizing that based on its greater structural similarity to MIBG, FPOIBG might be a better analogue than LMI1195.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Synthesis and evaluation of 4-[18F]fluoropropoxy-3-iodobenzylguanidine ([18F]FPOIBG): A novel 18F-labeled analogue of MIBG

Vaidyanathan

McDougald

Koumarianou

et al. 2015

Nuclear Medicine and Biology

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“…Some notable examples of these reagents are shown in Figure 2, together with the year in which they were reported. [8][9][10][11][12][13][14][15][16][17][18][19] Whilst it is true that some fluorinating agents begin to look exotic and expensive, they merely serve a purpose for the discovery of new molecules, often this is done with a late-stage 'fluorine scan'. Not every fluorination is going to give a 'better' molecule; in fact, it is quite the opposite, which is perhaps part of the excitement!…”

Section: Cluster Syn Lettmentioning

confidence: 99%

Cluster Preface: Progress in Organo-Fluorine Chemistry

Browne¹

2014

Synlett

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“…After our presentation of FLUOLEAD TM at Winter Fluorine Conference in January 2009, crystalline dialkylamidodifluorosulfinium tetrafluoroborates ([R 2 N + =SF 2 ]BF 4 À ) were reported to be useful deoxofluorinating agents when combined with Et 3 N(HF) 3 [114].…”

Section: O-(trifluoromethyl)dibenzofuranium Salts and Their Precursorsmentioning

confidence: 99%

Exploration of fluorination reagents starting from FITS reagents

Umemoto

2014

Journal of Fluorine Chemistry

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Aminodifluorosulfinium Tetrafluoroborate Salts as Stable and Crystalline Deoxofluorinating Reagents

Cited by 194 publications

References 23 publications

Synthesis and evaluation of 4-[18F]fluoropropoxy-3-iodobenzylguanidine ([18F]FPOIBG): A novel 18F-labeled analogue of MIBG

Synthesis and evaluation of 4-[18F]fluoropropoxy-3-iodobenzylguanidine ([18F]FPOIBG): A novel 18F-labeled analogue of MIBG

Cluster Preface: Progress in Organo-Fluorine Chemistry

Exploration of fluorination reagents starting from FITS reagents

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