Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf
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Synthesis, dynamic NMR characterization and XRD studies of novel N,N’-substituted piperazines for bioorthogonal labeling
Mamat, C.; Pretze, M.; Gott, M.; Köckerling, M.
Novel, functionalized piperazine derivatives were successfully synthesized and fully characterized by 1H/13C/19F NMR, MS, elemental analysis and lipophilicity. All piperazine compounds occur as conformers resulting from the partial amide double bond. Furthermore, a second conformational shape was observed for all nitro derivatives due to the limited change of the piperazine chair conformation. Therefore, two coalescence points were determined and their resulting activation energy barriers were calculated using 1H NMR. To support this result, single crystals of 1-(4-nitrobenzoyl)piperazine (3a, monoclinic, space group C2/c, a = 24.587(2), b = 7.0726(6), c = 14.171(1) Å, β = 119.257(8)°, V = 2149.9(4) Å3, Z = 4, Dobs = 1.454 g/cm3) and the alkyne derivative 4-(but-3-yn-1-yl)-1-(4-fluorobenzoyl)piperazine (4b, monoclinic, space group P21/n, a = 10.5982(2), b = 8.4705(1), c = 14.8929(3) Å, β = 97.430(1)°, V = 1325.74(4) Å3, Z = 4, Dobs = 1.304 g/cm3) were obtained from a saturated ethyl acetate solution. The rotational conformation of these compounds was also verified by XRD. As proof of concept for future labeling purposes, both nitropiperazines were reacted with [18F]F–. To test the applicability of these compounds as possible 18F-building blocks, two biomolecules were modified and chosen for conjugation either using the Huisgen-click reaction or the traceless Staudinger ligation.
Keywords: building blocks; coalescence; dynamic NMR; labeling; Staudinger ligation
Beilstein Journal of Organic Chemistry 12(2016), 2479-2489