Application of Methyl Bisphosphine‐Ligated Palladium Complexes for Low Pressure N‐¹¹C‐Acetylation of Peptides

Abstract

A mild and effective method is described for C-labeling of peptides selectively at the N-terminal nitrogen or at internal lysine positions. The presented method relies on the use of specific biphosphine palladium-methyl complexes and their high reactivity towards amino-carbonylation of amine groups in the presence [ C]carbon monoxide. The protocol facilitates the production of native N- C-acetylated peptides, without any structural modifications and has been applied to a selection of bioactive peptides.

From Carbon-11-Labeled Amino Acids to Peptides in Positron Emission Tomography: the Synthesis and Clinical Application

“…11 C]acetylated peptides on terminal amine or lysine residues was reported by Andersen et al The strength of this paper is that several N-acetylated peptides have been described, such as ) and proved to be Nterminal selective, however has a competing reaction on cysteine residues, namely the S-acetylation, might serve as an additional challenge for future applications [89].…”

Chemistry for Positron Emission Tomography: Recent Advances in 11C‐, 18F‐, 13N‐, and 15O‐Labeling Reactions

“…[42,43] In addition, aP d-mediated transmetalation of boronate precursors could allow 11 C-carbonylation with [ 11 C]CO (Scheme 5A2). [50] Several representative N-11 C-acetylated bioactive peptides,s uch as [ 11 C]lacosamide,[ 11 C]acetyl LULUPhol, and [ 11 C]acetyl cRGDfK were obtained in high RCYs of 33-46 %a nd ah igh molar activity of 281-404 GBq mmol À1 . 11 C-Labeled amides could also be obtained from appropriate primary or secondary amines in Pd-mediated crosscoupling reactions between aryl halides and [ 11 C]CO. [10][11][12][13][14] Several representative radiotracers are shown in Scheme 5B1.…”

“…Representative examples include ar etinoid compound [ 11 C]Am80 [44] and [ 11 C]aspirin, [45] which were obtained from the corresponding boronates. [50] Thes ynthesis of 11 C-carbonyl-labeled ketones can be accomplished by three-component Stille-type cross-coupling reactions involving [ 11 C]CO (Scheme 6A). This method is one of three primary methods to access 11 C-labeled amides,inaddition to [ 11 C]CO 2 (by acylation and aminolysis) and [ 11 C]CN (by controlled hydrolysis) methods.…”

Late‐Stage Isotopic Carbon Labeling of Pharmaceutically Relevant Cyclic Ureas Directly from CO2

“…Theuse of radiolabeled peptides and proteins as imaging tools for drug development and clinical diagnostics has recently attracted considerable attention. [24] In 2017, two major contributions from Buchwald, Hooker, and co-workers [24b] using H[ 11 C]CN as al abeled building block and from Antoni, Skrydstrup,and co-workers [24c] utilizing [ 11 C]CO were reported. Both methods use efficient metal catalysts for the insertion of the desired tag on as eries of peptides.C onsidering the high efficiencya nd orthogonality of the SAW sequence,w ea pplied it to ad esigned peptide sequence bearing the desired azido-amine group and most of the classical reactive moieties displayed by amino acids (alcohol, carboxylic acid, amine,a nd indole groups).…”