Stereoselective synthesis of E-64 and related cysteine proteases inhibitors from 2,3-epoxyamides.
The stereoselective synthesis of cathepsin inhibitors from indoline type epoxyamides is described. The use of this type of epoxyamides permitted the preparation of E-64 and CA-074 related compounds depending on the order in which the key steps, the oxidation of indoline amides to indole amides and oxidative acetal cleavage were undertaken. By taking advantage of the facile substitution of the indole of the corresponding indole epoxyamides, with various nucleophiles, we were able to prepare different epoxysuccinic acids derivatives as potential cathepsin inhibitors.
Sarabia
Francisco
F
Departamento de Bioquímica, Biología Molecular y Química Orgánica, Facultad de Ciencias, Universidad de Málaga, 29071 Málaga, Spain. frsarabia@uma.es
Sánchez-Ruiz
Antonio
A
Chammaa
Samy
S
D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D007930:Leucine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D013237:Stereoisomerism
D015853:Cysteine Proteinase Inhibitors; D007930:Leucine; C024974:E 64