title: Additional insights on the bastadins: isolation of analogues from the sponge Ianthella cf. reticulata and exploration of the oxime configurations.
abstract: The focus of this study is on the bastadin class of bromotyrosine derivatives, commonly isolated from Ianthella marine sponges, and is the first report on the secondary metabolites from Ianthella cf. reticulata. Two new bastadins were isolated, (E,Z)-bastadin 19 (1a), a diastereoisomer of the known (E,E)-bastadin 19 (1b), and dioxepine bastadin 3 (2), an unusual dibenzo-1,3-dioxepine. A bastadin NMR database was created and assisted in the structure determination of 1b and 2 and the rapid dereplication of 10 other known compounds including bastadins 2-9 (3-10), 13 (11), and 19 (1a). The geometry of the 2-(hydroxyimino)-N-alkylamide chains, a chemical feature present in all bastadins, was further probed, and new insights regarding the natural oxime configuration are discussed. Bastadins possessing (E,Z)-, (Z,E)-, or (E,E)-dioxime configurations could be artifacts of isolation or storage in solution. Therefore, this point was explored by photochemical and thermal isomerization studies, as well as molecular mechanics calculations. Bastadins 13 (11) and 19 (1a) exhibited moderate inhibition against Trypanosoma brucei, and bastadin 4 (5) was cytotoxic to HCT-116 colon cancer cells.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA.
authors.forename: Laurent
authors.initials: L
authors.lastname: Calcul
authors.forename: Wayne D
authors.initials: WD
authors.lastname: Inman
authors.forename: Alexi A
authors.initials: AA
authors.lastname: Morris
authors.forename: Karen
authors.initials: K
authors.lastname: Tenney
authors.forename: Joseline
authors.initials: J
authors.lastname: Ratnam
authors.forename: James H
authors.initials: JH
authors.lastname: McKerrow
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Valeriote
authors.forename: Phillip
authors.initials: P
authors.lastname: Crews
mesh_terms: D000818:Animals; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D055768:Halogenated Diphenyl Ethers / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010091:Oximes / Q000737:chemistry; D021261:Parasitic Sensitivity Tests; D011161:Porifera / Q000737:chemistry*; D013237:Stereoisomerism; D014346:Trypanosoma brucei brucei / Q000187:drug effects*
chemical_list: D055768:Halogenated Diphenyl Ethers; D010091:Oximes; C474669:bastadin 4