Multicomponent synthesis of dihydrobenzoxazepinones, bearing four diversity points, as potential α-helix mimics.
A very short convergent synthesis of dihydrobenzoxazepinones, bearing four diverse diversity points, based on coupling the Ugi reaction with a Mitsunobu cyclization, was developed. These compounds are potential α-helix mimics, where three of the four appendages are expected to imitate the residues in i, i + 4 and i + 7 positions. A library of 22 compounds bearing lipophilic substituents, designed to interact with the hydrophobic cleft of anti-apoptotic protein Bcl-xL, was synthesized. Preliminary biochemical tests, based on competitive binding, have already been carried out.
Banfi
Luca
L
Department of Chemistry and Industrial Chemistry, University of Genova, via Dodecaneso 31, 16146 Genova, Italy. banfi@chimica.unige.it
Basso
Andrea
A
Cerulli
Valentina
V
Guanti
Giuseppe
G
Lecinska
Paulina
P
Monfardini
Ilaria
I
Riva
Renata
R
D000438:Alcohols / Q000138:chemical synthesis / Q000737:chemistry; D002625:Chemistry, Organic / Q000379:methods*; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D020156:Salicylic Acid / Q000138:chemical synthesis / Q000737:chemistry
D000438:Alcohols; D006575:Heterocyclic Compounds, 3-Ring; D020156:Salicylic Acid