Synthesis and biological evaluation of a potent salicylihalamide A lactam analogue
- Author(s)
- Balan, D; Burns, CJ; Fisk, NG; Hugel, H; Huang, DCS; Segal, D; White, C; Wagler, J; Rizzacasa, MA;
- Details
- Publication Year 2012-10-28,Volume 10,Issue #40,Page 8147-8153
- Journal Title
- ORGANIC & BIOMOLECULAR CHEMISTRY
- Publication Type
- Journal Article
- Abstract
- The first synthesis of a lactam analogue 3 of salicylihalamide A (1) is reported. A key step in the approach was a photochemical acylation coupling between amine 10 and dioxinone 9 to form the amide 19. Acetylation followed by RCM with Grubbs 1st generation catalyst gave the desired E-lactam 23 (E : Z ratio 87: 13) as the major compound. Conversion of macrolactam 23 into the vinyl iodide 26 followed by Cu catalysed cross coupling with the diene amide 7 gave aza-salicylihalamide analogue 3 in good yield. This compound demonstrated potent activity against several human leukaemia cell lines.
- Publisher
- ROYAL SOC CHEMISTRY
- Keywords
- FORMAL TOTAL-SYNTHESIS; V-ATPASE INHIBITORS; VACUOLAR ATPASE; L-RHAMNOSE; D-GLUCOSE; (-)-SALICYLIHALAMIDE-A; METATHESIS; DISCOVERY; AMIDES
- Research Division(s)
- Chemical Biology
- Publisher's Version
- https://doi.org/10.1039/c2ob26649k
- Terms of Use/Rights Notice
- © Royal Society of Chemistry 2013
Creation Date: 2012-10-28 12:00:00