Synthesis and evaluation of eight-membered cyclic pseudo-dipeptides.
In the course of the development of calpain inhibitors, we report the synthesis of eight-membered cyclic pseudo dipeptides closely related to the known inhibitor SJA6017. The ring closure was effected by metathesis of the diallyl-substituted dipeptides 6 and 7. The formation of the dipeptides under kinetic control leads to the preferential formation of the unlike diastereomer 7 over the like diastereomer 6. The relative configuration of the diastereomers was determined by NMR and modeling studies of the related cyclic compounds 8 and 9 and their derivatives. The compounds proved not to inhibit calpain.
Abell
Andrew D
AD
Department of Chemistry, University of Canterbury, Private Bag 4800, Christchurch, New Zealand. andrew.abell@canterbury.ac.nz
Brown
Karina M
KM
Coxon
James M
JM
Jones
Matthew A
MA
Miyamoto
Sigeru
S
Neffe
Axel T
AT
Nikkel
Janna M
JM
Stuart
Blair G
BG
D002154:Calpain / Q000037:antagonists & inhibitors; D019295:Computational Biology; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D011487:Protein Conformation
D004151:Dipeptides; C109145:N-(4-fluorophenylsulfonyl)-L-valyl-L-leucinal; D010456:Peptides, Cyclic; D002154:Calpain