Synthesis of bilocularin A carbamate derivatives and their evaluation as leucine transport inhibitors in prostate cancer cells.

作者: Cohan Huxley , Mario Wibowo , Kah Yean Lum , Shelly Gordon , Sebastian D'Hyon

DOI: 10.1016/J.PHYTOCHEM.2020.112478

关键词:

摘要: Large-scale extraction of the leaves Australian rainforest tree Maytenus bilocularis followed by extensive purification studies afforded targeted and abundant dihydro-β-agarofuran, bilocularin A, in sufficient quantities (>500 mg) for detailed semi-synthetic chemistry. Eight A carbamate analogues were synthesised using a series commercially available isocyanate reagents high purity (>95%) variable yields (9-91%). All previously undescribed spectroscopically characterised NMR, UV, IR MS data. One compound crystalline material subsequent single crystal X-ray analysis (Cu-Kα) confirmed chemical structure along with absolute configuration. compounds evaluated anti-proliferative activity against human prostate cancer cell line LNCaP; none showed significant (>50%) growth inhibition at 20 μM. Compounds also tested their ability to inhibit leucine transport LNCaP cells, two moderate IC50 values 8.9 8.5 μM. This is first reported synthesis dihydro-β-agarofuran derivatives.

参考文章(39)
Rohan A. Davis, Gregory K. Pierens, Peter G. Parsons, Synthesis and spectroscopic characterisation of a combinatorial library based on the fungal natural product 3-chloro-4-hydroxyphenylacetamide. Magnetic Resonance in Chemistry. ,vol. 45, pp. 442- 445 ,(2007) , 10.1002/MRC.1984
Oliver Callies, María P. Sánchez-Cañete, Francisco Gamarro, Ignacio A. Jiménez, Santiago Castanys, Isabel L. Bazzocchi, Restoration of Chemosensitivity in P-Glycoprotein-Dependent Multidrug-Resistant Cells by Dihydro-β-agarofuran Sesquiterpenes from Celastrus vulcanicola Journal of Natural Products. ,vol. 78, pp. 736- 745 ,(2015) , 10.1021/NP500903A
George M. Sheldrick, Crystal structure refinement with SHELXL Acta Crystallographica Section C-crystal Structure Communications. ,vol. 71, pp. 3- 8 ,(2015) , 10.1107/S2053229614024218
Vanida Choomuenwai, Katherine T. Andrews, Rohan A. Davis, Synthesis and antimalarial evaluation of a screening library based on a tetrahydroanthraquinone natural product scaffold Bioorganic & Medicinal Chemistry. ,vol. 20, pp. 7167- 7174 ,(2012) , 10.1016/J.BMC.2012.09.052
Klaus Schwetlick, Rainer Noack, Kinetics and catalysis of consecutive isocyanate reactions. Formation of carbamates, allophanates and isocyanurates Journal of The Chemical Society-perkin Transactions 1. pp. 395- 402 ,(1995) , 10.1039/P29950000395
Emma C. Barnes, Vanida Choomuenwai, Katherine T. Andrews, Ronald J. Quinn, Rohan A. Davis, Design and synthesis of screening libraries based on the muurolane natural product scaffold Organic and Biomolecular Chemistry. ,vol. 10, pp. 4015- 4023 ,(2012) , 10.1039/C2OB00029F
Clare F. Macrae, Ian J. Bruno, James A. Chisholm, Paul R. Edgington, Patrick McCabe, Elna Pidcock, Lucia Rodriguez-Monge, Robin Taylor, Jacco van de Streek, Peter A. Wood, Mercury CSD 2.0 – new features for the visualization and investigation of crystal structures Journal of Applied Crystallography. ,vol. 41, pp. 466- 470 ,(2008) , 10.1107/S0021889807067908
Etienne Delebecq, Jean-Pierre Pascault, Bernard Boutevin, François Ganachaud, On the Versatility of Urethane/Urea Bonds: Reversibility, Blocked Isocyanate, and Non-isocyanate Polyurethane Chemical Reviews. ,vol. 113, pp. 80- 118 ,(2013) , 10.1021/CR300195N
Kristina Grabowski, Karl-Heinz Baringhaus, Gisbert Schneider, Scaffold diversity of natural products: inspiration for combinatorial library design Natural Product Reports. ,vol. 25, pp. 892- 904 ,(2008) , 10.1039/B715668P
Ruben G. G. Leenders, Rob Ruytenbeek, Eric W. P. Damen, Hans W. Scheeren, Highly diastereoselective synthesis of anomeric beta-O-glycopyranosyl carbamates from isocyanates Synthesis. ,vol. 1996, pp. 1309- 1312 ,(1996) , 10.1055/S-1996-4377