Solid phase organic synthesis of piperazinone containing enkephalin mimetics: a readily derivatized, traceless scaffold.
The solid phase synthesis of a series of piperazinone-derived Leu-enkephalin analogues is presented. The initial step in the synthesis involved the N-alkylation of Wang resin bound N-(4-tert-butyloxy-phenethyl)-glycine with D or L Boc-serine-beta-lactone (the Vederas lactone). The resulting carboxylic acid was then coupled to a variety of monosubstituted benzylamine derivatives using benzotriazol-1-yloxy-tris(dimethyl-amino)phosphonium hexafluorophosphate (the BOP reagent) to yield a series of resin bound tertiary amides. Treatment with 5% H2O in TFA resulted in the facile cleavage, deprotection, and cyclization of this linear precursor to yield a series of piperazinones (compounds 1-8).
Shreder
K
K
Department of Chemistry, University of California at San Diego, La Jolla 92093-0343, USA.
Zhang
L
L
Gleeson
J P
JP
Ericsson
J A
JA
Yalamoori
V V
VV
Goodman
M
M
D015195:Drug Design; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D019151:Peptide Library; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry*; D012116:Resins, Plant; D016339:Spectrometry, Mass, Fast Atom Bombardment
D019151:Peptide Library; D010879:Piperazines; D012116:Resins, Plant; D004743:Enkephalin, Leucine