Total synthesis of syringolin A and B.
Total syntheses of two recently discovered proteasome inhibitors, syringolin A and B, are reported. The key to our approach was creation of the alpha,beta-unsaturated 12-membered lactam via intramolecular Horner-Wadsworth-Emmons reaction. Such reactions have been broadly used to prepared macrolactones, but this work presents a rarer example of its application to macrolactams. The final steps involved attachment of the bis(valinyl)urea side chain using peptide coupling procedures, including a method based on the unprotected valine N-carboxy anhydride. The additional alkene of syringolin A was created through cross-metathesis.
Pirrung
Michael C
MC
Department of Chemistry, University of California, Riverside, California 92521, USA. michael.pirrung@ucr.edu
Biswas
Goutam
G
Ibarra-Rivera
Tannya R
TR
D008968:Molecular Conformation; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D061988:Proteasome Inhibitors; D013237:Stereoisomerism; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
D010456:Peptides, Cyclic; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; C407267:syringolin A; C540864:syringolin B; D014508:Urea