title: An efficient synthesis of an exo-enone analogue of LL-Z1640-2 and evaluation of its protein kinase inhibitory activities.
abstract: An efficient synthesis of an exo-enone analogue (5) of resorcylic acid lactone (RAL), natural product LL-Z1640-2 (1), has been achieved using a Ni-catalysed regioselective reductive coupling macrocyclisation of an alkyne-aldehyde as a key step. The synthetic route is significantly shorter than those for the natural product and avoids the isomerisation problem of the cis-double bond in the molecule. The preliminary biological evaluation showed that the exo-enone analogue is a potent inhibitor of several important kinases relevant to cancer drug development.
authors.affiliation: Institute of Chemical and Engineering Sciences (ICES), Agency for Science, Technology and Research (A*STAR), 8 Biomedical Grove, Neuros #07-01, Singapore 138665. chen_anqi@ices.a-star.edu.sg.
authors.forename: Stephanie Q
authors.initials: SQ
authors.lastname: Wang
authors.forename: Shermin S
authors.initials: SS
authors.lastname: Goh
authors.forename: Christina L L
authors.initials: CLL
authors.lastname: Chai
authors.forename: Anqi
authors.initials: A
authors.lastname: Chen
mesh_terms: D004305:Dose-Response Relationship, Drug; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010770:Phosphotransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D007659:Ketones; C118715:LL Z1640-2; D007783:Lactones; D047428:Protein Kinase Inhibitors; D010770:Phosphotransferases