Isotopic methylation

Abstract

SummaryThis review reports recent methods by which organic compounds, and especially pharmaceuticals, have been isotopically labelled by the incorporation of carbon or hydrogen isotopes in methylation processes. Particular attention is paid to the incorporation of carbon-11; both the synthesis of such labelled methylating agents and applications of their use are discussed. The review has reported reagents and conditions by which a number of organic compounds have been obtained recently. It also assesses the limitations of reported methods and proposes some alternative techniques and innovations.The application of catalysts such as Ag + and conditions such as microwave irradiation to encourage these reactions are also included, with suggestions of other, potentially beneficial, ways to assist them. In many cases, the radio-chemical yield and purity of the labelled product are given along with an estimate of the total reaction time.

5-Pyrrolidinylsulfonyl Isatins as a Potential Tool for the Molecular Imaging of Caspases in Apoptosis

“…Our preliminary radiolabeling attempts resulted in the radiolabeled 5-pyrrolidinylsulfonyl isatin derivative [ 125 I] 26 . In future studies, the synthesized precursors 7 , 8 , 17 , 18 , 23 , 24 , 31 , and 32 will be radiolabeled with different radionuclides, including iodine-123, fluorine-18, or carbon-11, which are typically used for noninvasive scintigraphic imaging using SPECT and PET. − This should result in lead candidate CBRs capable of intracellular targeting early stages of the apoptotic process. Caspase activation occurs in all settings of clinically relevant apoptosis, such as that in acute myocardial infarction, chronic heart failure, allograft rejection, stroke, neurodegenerative disorders, induction of apoptosis by chemotherapy or irradiation, and in other pathological conditions. − If successfully applied in clinical diagnostic algorithms in the future, the CBRs could represent the first synthetic nonpeptidyl biomarkers (radiotracers) that can exclusively and noninvasively detect apoptotic tissues in vivo.…”

Synthesis of 11C, 18F, 15O, and 13N Radiolabels for Positron Emission Tomography

“…The synthetic methods used to carry out methylation reactions are relatively straightforward and usually involve simply trapping [ 11 C]CH 3 I in a solution of the target precursor and heating for a short time (typically < 5 min). Many 11 C-methylation procedures are reported in the literature [54] and the method is used for the production of the key 11 C tracers (Scheme 3): Pittsburg Compound B ([ 11 C]PIB, 1) for imaging amyloid plagues in Alzheimers disease, [17,50,55,56] raclopride (2) [57,58] and [ 11 C]N-methylspiperone [59] ([ 11 C]NMSP, 3) for imaging of the dopamine receptor, [60] [ 11 C]N-methylpiperidin-4-yl propinoate ([ 11 C]PMP, 4) for mapping acetylcholinesterase activity in patients with Alzheimers disease, [61] [ 11 C]flumazanil (5) for imaging benzodiazepine receptors, [62] and the opioid receptor ligand [ 11 C]carfentanil (6). [21,63,64] In recent years the use of transition-metal-mediated methylation reactions has become more widespread for 11 C radiolabeling, especially notable is the use of palladium catalysts for the formation of a CÀ 11 C bond by adapted Stille and Suzuki coupling reactions.…”

Recent progress in [11C]carbon dioxide ([11C]CO2) and [11C]carbon monoxide ([11C]CO) chemistry

“…Due to its simplicity, 11 C-methylation is widely used for research and clinical production of functionalised 11 C-tracers as extensively reviewed in the literature. 2,4,5,[10][11][12][13][14][15][16][17][18] The recent development of "loop" chemistry has enabled technical and yield improvements in 11 C-methylation reactions. 2 "Loop" 11 C-methylation involves depositing a solution of the reagents in a thin film on the inside of an HPLC loop.…”