Synthesis of bilocularin A carbamate derivatives and their evaluation as leucine transport inhibitors in prostate cancer cells
Cohan Huxley, Mario Wibowo, Kah Yean Lum, Shelly Gordon, Sebastian D'Hyon, Hanyu Guan, Xueyi Wang, Yuxi Chen, Mingran Si, Mengchao Wang, Jonathan M White, Kanu Wahi, Qian Wang, Jeff Holst, Rohan A Davis
Phytochemistry | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2020
Large-scale extraction of the leaves of the Australian rainforest tree Maytenus bilocularis followed by extensive purification studies afforded the targeted and abundant dihydro-β-agarofuran, bilocularin A, in sufficient quantities (>500 mg) for detailed semi-synthetic chemistry. Eight bilocularin A carbamate analogues were synthesised using a series of commercially available isocyanate reagents in high purity (>95%) and variable yields (9-91%). All previously undescribed analogues were spectroscopically characterised using NMR, UV, IR and MS data. One compound afforded crystalline material and subsequent single crystal X-ray analysis (Cu-Kα) confirmed the chemical structure along with the a..View full abstract
Awarded by National Health and Medical Research Council (NHMRC)
Awarded by Australian Research Council (ARC)
The authors acknowledge the National Health and Medical Research Council (NHMRC) for financial support (Grant APP1024314 to R.A.D.) and thank the Australian Research Council (ARC) for support towards NMR and MS equipment (Grant LE140100119, LE0668477 and LE0237908) and financial support (Grant LP120200339 to R.A.D.). R.A. D. holds a New Concept Grant funded by It's a Bloke Thing through the Prostate Cancer Foundation of Australia's Research Program. This study was also supported by the Movember Revolutionary Team Award Targeting Advanced Prostate Cancer (Q.W. and J.H.) and the Australian Government Department of Health. K.Y.L. and M.W. thank Griffith University for Ph.D. scholarships (GUPRS and GUIPRS).