New fluorinated peptidomimetics through tandem aza-michael addition to alpha-trifluoromethyl acrylamide acceptors: synthesis and conformational study in solid state and solution.
A range of partially modified retro (PMR) psi[NHCH(2)] peptide mimetics containing a hydrolytically stable CH(2)CH(CF(3))CO unit have been synthesized. The first kind of peptidomimetics is obtained from the highly efficient aza-Michael addition of different amines to alpha-trifluoromethyl acrylamide acceptors. Subsequent deprotection of the amino group furnishes the key common intermediate for the synthesis of other families of peptidomimetics: dipeptides, tripeptides, peptidomimetics containing a urea moiety, and structures containing two units of alpha-trifluoromethyl-beta(2)-alanine. Finally, a conformational study of several of the newly synthesized peptidomimetics, performed with the aid of X-ray analysis and NMR techniques, shows a beta-turn-like conformation for the structures both in the solid state and in solution.
Fustero
Santos
S
Departamento de Quimica Organica, Universidad de Valencia, 46100 Burjassot, Valencia, Spain. santos.fustero@uV.es
Chiva
Gema
G
Piera
Julio
J
Sanz-Cervera
Juan F
JF
Volonterio
Alessandro
A
Zanda
Matteo
M
Ramirez de Arellano
Carmen
C
D000178:Acrylamides / Q000737:chemistry*; D000409:Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D001372:Aza Compounds / Q000737:chemistry*; D018360:Crystallography, X-Ray; D017611:Fluorine Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D012996:Solutions
D000178:Acrylamides; D001372:Aza Compounds; D017611:Fluorine Compounds; D010455:Peptides; D012996:Solutions; C542738:alpha-trifluoromethyl acrylamide; C507723:alpha-trifluoromethylalanine; D000409:Alanine