2024-03-28T08:53:24Zhttps://repositori.uji.es/oai/requestoai:repositori.uji.es:10234/224302023-06-14T12:03:37Zcom_10234_7053com_10234_9col_10234_8639
00925njm 22002777a 4500
dc
Alfonso Rodríguez, Ignacio
author
Bolte, Michael
author
Bru Roig, Miriam
author
Burguete, M. Isabel
author
Luis, Santiago V.
author
2008
The efficient synthesis of large-ring pseudopeptidic macrocycles through a multicomponent [2+2] reductive amination reaction is described. The reaction was entirely governed by the structural information contained in the corresponding open-chain pseudopeptidic bis(amidoamine) precursors, which have a rigid (R,R)-cyclohexane-1,2-diamine moiety. A remarkable match/mismatch relationship between the configurations of the chiral centers of the cyclic diamine and those of the peptidic frame was observed. The macrocyclic tetraimine intermediates have been studied in detail by NMR spectroscopy, circular dichroism (CD), and molecular modeling, and the results support the appropriate preorganization induced by the match combination of the chiral centers. We have also synthesized the corresponding open-chain bis(imine) model compounds. The structural studies (NMR spectroscopy, CD, modeling) of these systems showed an intrinsically lower reactivity of the mismatch combination, even when the product of the reaction was acyclic. In addition, a synergistic effect between the two chiral substructures for the correct folding of the molecules was observed. Finally, X-ray analysis of the HCl salt of one of the macrocycles showed an interesting pattern; the macrocyclic rings stack in columnar aggregates leaving large interstitial channels filled with water-solvated chloride anions
ALFONSO RODRÍGUEZ, Ignacio, et al. Designed folding of pseudopeptides: the transformation of a configurationally driven preorganization into a stereoselective multicomponent macrocyclization. Chemistry : a European journal, 2008, v. 14, n. 29 p. 8879-8891
0947-6539
http://hdl.handle.net/10234/22430
Macrocycles
Peptidelike structures
Conformation
Preorganization
Foldamers
Designed folding of pseudopeptides: the transformation of a configurationally driven preorganization into a stereoselective multicomponent macrocyclization