Synthesis and metal complexation properties of Ph-DTPA and Ph-TTHA: novel radionuclide chelating agents for use in nuclear medicine.

We wish to report the synthesis and metal complexation properties of new radionuclide chelating agents for use in nuclear medicine. The strategy includes the facile preparation of rigid analogues of DTPA and TTHA possessing an aromatic ring. The aromatic structure used increased the stability of the complexes formed (pre-organization concept) and they are easily functionalised for attaching to any support. The poly(amino)poly(carboxylic) acids, Ph-DTPA (5a) and Ph-TTHA (5b) were obtained in five steps from phenylenediamine as the starting material with overall yields of 42 and 20%, respectively. The key step in this synthetic process is the preparation of tri- and tetra-amino compounds, 3a and 3b, respectively. In order to assess the ability of both ligands to complex with different metals ((111)In, (153)Sm, (90)Y, (177)Lu, (213)Bi, (225)Ac), along with their suitability for use in nuclear medicine, we used a number of complementary tests. We were able to demonstrate the high complexation capacity of Ph-DTPA (5a) with a broad range of radionuclides in a slightly acidic medium. In vitro stability studies show the high stability of Ph-DTPA with (111)In in human serum, a necessary condition for all medical applications. The protonation constant (log K(H)(i)) of Ph-DTPA (5a) was determined by potentiometric methods.

An efficient route to pyrimidine nucleoside analogues by [4 + 2] cycloaddition reaction.

We report here an efficient synthesis for pyrimidine nucleoside analogues by [4 + 2] cycloaddition reaction. These compounds were obtained by convergent chemistry from glycosyl isothiocyanates 3a-f (pyranoses, furanoses, and dissaccharides) and diazadienium salt 5. In fact, diazapentadienium iodide 5 prepared from vinylthioamide 4 is an efficient intermediate in heterocyclic synthesis and reacts with isothiocyanates 3a-f affording beta-D-uracil analogues 7a-f in good yields and with total regiocontrol. All compounds were fully characterized by IR, HRMS, and 13C and 1H NMR (COSY and HMQC).

From thiourea to bicyclic structures: an original route to imidazo[2,1-b]thiazoles, 5H-thiazolo[3,2-a]pyrimidines, 7H-imidazo[2,1-b][1,3]thiazines, and 2H,6H-pyrimido[2,1-b][1,3]thiazines.

We report an example of an efficient regioselective synthesis of biheterocyclic compounds using thiourea as starting material. In fact, N,N'-bis(dimethylaminomethylene)thiourea (1), easily prepared by double condensation of N,N-dimethylformamide dimethyl acetal with thiourea, can be reacted with haloketones or acrylic dienophiles to give thiazolic (2) and thiazinic (3) diazadienes, respectively, themselves undergoing cyclization reactions to yield imidazo[2,1-b]thiazoles, 5H-thiazolo[3,2-a]pyrimidines, 7H-imidazo[2,1-b][1,3]thiazines, and 2H,6H-pyrimido[2,1-b][1,3]thiazines without any regioisomeric ambiguity. This straightforward route represents an original and unambiguously regioselective pathway to these valuable heterocycles.