title: Full control of the regiospecific N-functionalization of C-functionalized cyclam bisaminal derivatives and application to the synthesis of their TETA, TE2A, and CB-TE2A analogues.
abstract: We describe an easy synthesis of original C-functionalized cyclam derivatives based on the efficient bisaminal template method. In the perspective of developing bifunctional chelating agents (BCAs), this new synthetic strategy offers the possibility of introducing various coupling functions on one carbon atom in the β-N position of the macrocycle, leaving the four nitrogen atoms available for the introduction of pendant coordinating arms. The methodology is based on a keystone C-functionalized oxo-cyclam bisaminal intermediate that is obtained by cyclization of a preorganized tetraamine using various methyl acrylate analogues. These compounds constitute valuable precursors for selective preparation of mono- and di-N-protected C-functionalized cyclams and C-functionalized cyclams, cross-bridged cyclams, and oxo-cyclam derivatives. This approach was successfully adapted to the synthesis of three BCAs with great interest especially for biomedical applications: TETA, TE2A, and CB-TE2A. The structures of different intermediates and Cu(II) complexes of C-functionalized cyclam derivatives were confirmed using single-crystal X-ray diffraction, while reactivity of the key intermediates was rationalized by the analysis of the electrostatic potentials calculated at the TPSSh/6-311G(d,p) level.
authors.affiliation: Université de Brest , UMR-CNRS 6521/SFR148 ScInBioS, UFR Sciences et Techniques, 6 Avenue Victor le Gorgeu, C.S. 93837, 29238 Brest, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Camus
authors.forename: Zakaria
authors.initials: Z
authors.lastname: Halime
authors.forename: Nathalie
authors.initials: N
authors.lastname: Le Bris
authors.forename: Hélène
authors.initials: H
authors.lastname: Bernard
authors.forename: Carlos
authors.initials: C
authors.lastname: Platas-Iglesias
authors.forename: Raphaël
authors.initials: R
authors.lastname: Tripier
mesh_terms: D002614:Chelating Agents / Q000737:chemistry*; D056831:Coordination Complexes / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D047028:Macrocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D014961:X-Ray Diffraction
chemical_list: D002614:Chelating Agents; D056831:Coordination Complexes; D006571:Heterocyclic Compounds; D047028:Macrocyclic Compounds; C024560:cyclam; D003300:Copper