212115-96-3Relevant academic research and scientific papers
Total synthesis of syringolin A
Dai, Chunhui,Stephenson, Corey R. J.
supporting information; experimental part, p. 3453 - 3455 (2010/10/02)
(Equation Presented). A convergent, efficient synthesis of syringolin A has been accomplished in 13 steps from commercially available materials, Garners aldehyde and l-valine. The unnatural 3,4-dehydrolysine fragment was prepared using successive Johnson-Claisen/Curtius rearrangement reactions. The macrolactamization and late-stage introduction of the side chain will provide convenient access to analogues of this promising proteasome inhibitor.
Total synthesis of syringolin A and B
Pirrung, Michael C.,Biswas, Goutam,Ibarra-Rivera, Tannya R.
supporting information; experimental part, p. 2402 - 2405 (2010/07/17)
Total syntheses of two recently discovered proteasome inhibitors, syringolin A and B, are reported. The key to our approach was creation of the α,β-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.
Convergent synthesis and biological evaluation of syringolin a and derivatives as eukaryotic 20S proteasome inhibitors
Clerc, Jerome,Schellenberg, Barbara,Groll, Michael,Bachmann, Andre S.,Huber, Robert,Dudler, Robert,Kaiser, Markus
experimental part, p. 3991 - 4003 (2010/10/02)
A convergent synthesis of SylA was developed and consists of the synthesis of a fully functionalized macrocycle, which is subsequently coupled with a urea moiety. For cyclization, ring-closing metathesis of a conformationally preorganized precursor was employed. The established synthetic route was then applied to the synthesis of SylA derivatives by using various peptidic side chains for decoration of the SylA macrocycle. The resulting collection of SylA analogues was tested for proteasome inhibition, revealing PEGylated SylA derivatives as the most potent proteasome inhibitors.
