title: Synthesis and biological evaluation of a potent salicylihalamide A lactam analogue.
abstract: The first synthesis of a lactam analogue 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.
authors.affiliation: School of Applied Sciences [Applied Chemistry], RMIT University, Bowen Street, Melbourne, Vic. 3001, Australia.
authors.forename: Dan
authors.initials: D
authors.lastname: Balan
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Burns
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Fisk
authors.forename: Helmut
authors.initials: H
authors.lastname: Hügel
authors.forename: David C S
authors.initials: DC
authors.lastname: Huang
authors.forename: David
authors.initials: D
authors.lastname: Segal
authors.forename: Charlotte
authors.initials: C
authors.lastname: White
authors.forename: Jörg
authors.initials: J
authors.lastname: Wagler
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rizzacasa
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D007769:Lactams / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007769:Lactams; C410986:salicylihalamide A