182621-36-9Relevant articles and documents
Total synthesis of hapalosin and two ring expanded analogs
Hermann, Christoph,Pais, Godwin C.G,Geyer, Armin,Kühnert, Sven M,Maier, Martin E
, p. 8461 - 8471 (2000)
The macrocyclic depsipeptide hapalosin was assembled from three subunits. Beginning with the condensation of a protected β-hydroxy acid 13 with the α-hydroxy ester 14, the hydroxy diester 16 was produced. This compound, in turn, was condensed with the γ-amino-β-hydroxy acid 17. Macrocyclization was performed on the fully deprotected amino acid 20. In a similar manner, a cyclization substrate 28 was prepared that contains valine instead of the α-hydroxy acid. In this case, however, the cyclization with the Shioiri reagent induced a Curtius rearrangement prior to the cyclization reaction. As a result the two ring expanded hapalosin analogs 29 and 30 were formed. The conformations of the three macrocycles were studied by 2D NMR spectroscopy and molecular dynamics simulation. It was found that in DMSO-d6 all of them prefer the s-trans-amide rotamer around the tertiary amide. (C) 2000 Elsevier Science Ltd.
Structure-activity relationships of rationally designed AMACR 1A inhibitors
Yevglevskis, Maksims,Lee, Guat L.,Nathubhai, Amit,Petrova, Yoana D.,James, Tony D.,Threadgill, Michael D.,Woodman, Timothy J.,Lloyd, Matthew D.
, p. 145 - 154 (2018/05/22)
α-Methylacyl-CoA racemase (AMACR; P504S) is a promising novel drug target for prostate and other cancers. Assaying enzyme activity is difficult due to the reversibility of the ‘racemisation’ reaction and the difficulties in the separation of epimeric prod
Syntheses of hapalosin analogs by solid-phase assembly of acyclic precursors
Hermann, Christoph,Giammasi, Chiara,Geyer, Armin,Maier, Martin E
, p. 8999 - 9010 (2007/10/03)
The paper details the synthesis of hapalosin analogs 4 (cyclic depsipeptides) using solid-phase chemistry. Key building blocks were the Fmoc-protected γ-amino-β-hydroxy acid 11 and the THP-protected syn-β-hydroxy acids 18. The amino acid 11 was fashioned from the amine 6 which was obtained by an ADH-route. The protected amino acids 18 were prepared by Evans aldol reactions. Esterification of 18 with the Wang resin started the solid-phase assembly of the depsipeptides 25 containing all the building blocks. A final solution-phase deprotection of the amino group followed by macrolactamization completed the synthesis of the analogs 4. In one instance (compound 4aaa) the conformation was studied using ROESY NMR spectroscopy and MD simulation. This revealed an almost complete (93:7) preference for the s-cis-rotamer.
