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 was 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 (1b), a diastereoisomer of the known (E,E)-bastadin 19 (1a), 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, 2 and the rapid dereplication of ten 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.

Qualitative variation in colour morphotypes of Ianthella basta (Porifera: Verongida)

“…Recent research effort has focused on whether these associated microbes may be responsible for the production of some of the biologically active secondary metabolites found in sponge taxa (Taylor et al, 2007). For instance, species of the family Ianthellidae are characterised by the presence of biologically active, colourless, brominated tyrosine-derived macrocyclic molecules, so-called bastadins (Calcul et al, 2010). Sponges of this family display a number of different morphologies and have a wide geographical distribution.…”

Unraveling the Bastarane and Isobastarane Oximo Amide Configurations and Associated Macrocycle Conformations: Implications of Their Influence on Bioactivities

“…We next examined the 1 H NMR chemical shifts and coupling constants of the methylene and amide protons for 1a - 1d to determine if there was any intramolecular hydrogen bonding between two oximo amides and/or other functional groups within the macrocycle that would impart rigidity 12. All chemical shifts for each methylene were isochronous, indicative of a flexible macrocyle.…”

“…Schmitz postulated “that either E , Z (or the Z , Z isomer thereof) is the natural metabolite and that isomerization during extraction, extract storage, and/or chromatography results in E , E being isolated as the predominant product.” Until recently, all bastadin metabolites have been reported with the ( E , E )-dioximo amide configuration. The single exception is represented in our recent description of the known ( E , E )-bastadin 19 ( 1a ), accompanied by ( E , Z )-bastadin 19 ( 1b ) 12. We were intrigued by the rare occurrence of the ( Z )-oximo amide in psammaplins and bastadins especially given the numerous publications on these metabolites , whereas biosynthetic work on nocardicins revealed the oxime biosynthethic pathway proceeded syn to the amide yielding a ( Z )-oximo amide 13,14.…”

The structural diversity and promise of antiparasitic marine invertebrate-derived small molecules

“…The 133 compounds included in this collection, discovered from 2008 to 2010, all displayed an IC 50 below 30 μM against one or more parasites during in vitro screening. It is evident that marine sponges provide the majority of antiparasitic MDSMs with 87 compounds included in 30 publications between 2008 and 2010 [11–14,15•,16,17,18•,19,20•,21–27,28•,29–31,32•,33,34•,35,36•,37•,38•,39•,40]. Marine-derived fungi have produced the next largest set of 20 compounds, reported in only four papers [41–44] and cyanobacteria follow with 11 compounds included in eight reports [45–52].…”

“…Halogenated metabolites [13,14,16,19,24,28•,33,40]. Secondary metabolites containing halogen atoms are commonly isolated from marine organisms and these compounds often elicit biological responses.…”