Macrocyclic 14-membered ring diketal diamines: Synthesis, conformational analysis and 99m Tc radiolabeling evaluation

Radouane Affani (1) , Philippe Auzeloux (2) , Jean-Claude Madelmont (2) , Denise Dugat (1)

1 SEESIB - Synthèse et étude de systèmes à intêret biologique
2 Etude Métabolique des Molécules Marquées

Chiral and achiral macrocyclic diketal diamines, analogs of cyclams, were synthesized from the previously obtained corresponding diketal dilactams by reduction with lithium aluminum hydride in the presence of a trace amount of triethylamine. In the (15-30) × 10-3 M concentration range, the reaction led mainly to the expected doubly reduced compounds except in the trans-OMe substituted series (R = Ph, Me), in which it partially stopped at the single reduction stage. A conformational study conducted by liquid NMR spectroscopy and molecular mechanics calculations showed that the most stable conformations were either set in a rectangular [3434]-type structure for trans-OMe compounds 7b (R = Me) and 10b (R = H) or stabilized by two intramolecular NH···O hydrogen bonds for all the other macrocyclic diamines. Tc-99m radiolabeling with the nitrido-technetium core [TcN]2+ gave 10-20 % exchange yields

Mots clés: Amines; Macrocycles; Reduction; Conformation analysis; Chelates; Technetium

Domaines: Chimie organique

Radouane Affani, Philippe Auzeloux, Jean-Claude Madelmont, Denise Dugat. Macrocyclic 14-membered ring diketal diamines: Synthesis, conformational analysis and 99m Tc radiolabeling evaluation. European Journal of Organic Chemistry, 2008, pp.2039-2048. ⟨hal-00270325⟩