Efficient macrocyclization of U-turn preorganized peptidomimetics: the role of intramolecular H-bond and solvophobic effects.
Simple peptidomimetic molecules derived from amino acids were reacted with meta- and para-bis(bromomethyl)benzene in acetonitrile to very efficiently yield macrocyclic structures. The cyclization reaction does not require high dilution techniques and seems to be insensitive to the size of the formed macrocycle. The analysis of data obtained by (1)H NMR, single-crystal X-ray diffraction, fluorescence measurements, and molecular mechanics indicate that folded conformations can preorganize the system for an efficient cyclization. The role played by intramolecular hydrogen-bonding and solvophobic effects in the presence of folded conformations is analyzed.
Becerril
Jorge
J
Department of Inorganic and Organic Chemistry, University Jaume, I. E-12080 Castellón, Spain.
Bolte
Michael
M
Burguete
M Isabel
MI
Galindo
Francisco
F
García-España
Enrique
E
Luis
Santiago V
SV
Miravet
Juan F
JF
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D040761:Biomimetic Materials / Q000737:chemistry*; D003198:Computer Simulation; D003500:Cyclization; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D012997:Solvents; D013050:Spectrometry, Fluorescence; D014050:Toluene / Q000031:analogs & derivatives; D014961:X-Ray Diffraction
D000577:Amides; D000596:Amino Acids; D010455:Peptides; D012997:Solvents; D014050:Toluene