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

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 triethylamme. In the (15-30) x 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 center dot center dot center dot O hydrogen bonds for all the other macrocyclic diamines. Tc-99m radiolabeling with the nitrido-technetium core [TcN](2+) gave approximate to 10-20% exchange yields. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)