title: Synthesis and conformational analysis of cyclic homooligomers from pyranoid ε-sugar amino acids.
abstract: New pyranoid ε-sugar amino acids were designed as building blocks, in which the carboxylic acid and the amine groups were placed in positions C2 and C3 with respect to the tetrahydropyran oxygen atom. By using standard solution-phase coupling procedures, cyclic homooligomers containing pyranoid ε-sugar amino acids were synthesized. Conformation analysis was performed by using NMR spectroscopic experiments, FTIR spectroscopic studies, X-ray analysis, and a theoretical conformation search. These studies reveal that the presence of a methoxy group in the position C4 of the pyran ring produces an important structural change in the cyclodipeptides. When the methoxy groups are present, the structure collapses through interresidue hydrogen bonds between the oxygen atoms of the pyran ring and the amide protons. However, when the cyclodipeptide lacks the methoxy groups, a U-shape structure is adopted, in which there is a hydrophilic concave face with four oxygen atoms and two amide protons directed toward the center of the cavity. Additionally, we found important evidence of the key role played by weak electrostatic interactions, such as the five-membered hydrogen-bonded pseudocycles (C5) between the amide protons and the ether oxygen atoms, in the conformation equilibrium of the macrocycles and in the cyclization step of the cyclic tetrapeptides.
authors.affiliation: Instituto de Productos Naturales y Agrobiología-CSIC, Avda. Astrofísico Francisco Sánchez, 3, 38206-La Laguna, Tenerife (Spain), Fax: (+34) 922-260135.
authors.forename: Andrés
authors.initials: A
authors.lastname: Feher-Voelger
authors.forename: Jorge
authors.initials: J
authors.lastname: Borges-González
authors.forename: Romen
authors.initials: R
authors.lastname: Carrillo
authors.forename: Ezequiel Q
authors.initials: EQ
authors.lastname: Morales
authors.forename: Javier
authors.initials: J
authors.lastname: González-Platas
authors.forename: Tomás
authors.initials: T
authors.lastname: Martín
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000606:Amino Sugars / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008968:Molecular Conformation
chemical_list: D000596:Amino Acids; D000606:Amino Sugars
keywords: conformation analysis; cyclic peptides; noncovalent interactions; solid-state structures; sugar amino acids