Rotational Energy Barrier around the C1–C11 Single Bond in Lamellarins: A Study by Variable-Temperature NMR

Fukuda, Tsutomu; Itoyama, Ryosuke; Minagawa, Terufusa; Iwao, Masatomo

doi:10.3987/com-13-s(s)69

Cited by 7 publications

(1 citation statement)

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“…310 Molecular modelling and variable-temperature NMR calculations suggested the barrier to rotation within various lamellarins is typically on the order of 72-87 kJ mol -1 , depending on substitution patterns, thus this semi-restricted rotation about the C-1 to C-11 bond is typically a thermally facile process resulting in racemisation. 311 There have been no…”

Section: -Atropisomerism Of Lamellarinsmentioning

confidence: 99%

Chemical Investigations of Pacific Marine Organisms

Bracegirdle¹

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This thesis describes a comparative study of three screening methods for the discovery of new marine natural products (MNP) from South Pacific organisms. Over the course of the study, 13 tunicates, one bryozoan and one red alga collected from the waters of the Kingdom of Tonga and New Zealand were investigated. Bioassay, ¹H nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) were used to prioritise six organisms for investigation, which resulted in the isolation and characterisation of 16 new and 11 previously reported metabolites. An NMR–based spectroscopic screening protocol led to the isolation of the new cyclic polyhalogenated monoterpene costatone C (46), isolated from a NZ red alga identified as Plocamium angustum, which showed moderate antibacterial activity. The absolute configuration of a previously reported and co–isolated bis–normonoterpene (47) was also deduced using Mosher’s method. The NMR screening protocol also prioritised the Tongan bryozoan Nelliella nelliiformis, from which the nucleosides nellielloside A and B (61 and 62) were isolated and inspired the synthesis of congeners 66–69. All six compounds showed potent kinase inhibitory activity against a subset of disease–relevant kinases, with IC50 values determined to be in the nM range for GSK3A, MAPK14 and RSK2. An MS screening protocol was also employed utilising molecular networking through the GNPS platform. Of the eight tunicates examined, three were further investigated based on promising constellations in the network, and collectively led to the identification of 13 new compounds. A new aromatic ketone (28) was isolated from the NZ tunicate Distaplia stylifera, while a comprehensive examination of a NZ Synoicum kuranui sample resulted in two new compounds, rubrolides T and U (110 and 111). The encrusting tunicate Didemnum ternerratum was the most fruitful organism examined in this work, resulting in the isolation of ten new and three previously reported lamellarin sulfates (147–151 and 153–156). The absolute configurations of atropisomers 148–151 were determined by comparison of experimental and calculated ECD spectra. Compound 151 showed moderate cytotoxicity against HCT–116 cells. This work illustrated the power of molecular networking as a screening tool when applied to the MNP field, particularly for the isolation new derivatives within a previously known family of compounds. It also suggested that the more traditional NMR spectroscopy–based screening protocol is still very useful as a standalone method when no comparative standards are available. These complementary techniques should be used together to maximise new MNP discovery.

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Section: -Atropisomerism Of Lamellarinsmentioning

confidence: 99%