Nebulosins: Trisubstituted Thiolane Natural Products from the Northeastern Atlantic Annelid Eupolymnia nebulosa

Abstract

Using both multi-informative molecular network and score-based approaches as prioritization strategies, the Northeastern Atlantic marine terebellid Eupolymnia nebulosa was selected for in-depth chemical investigation. A family of 16 new metabolites named nebulosins was isolated and structurally characterized from extensive analyses of HRMS/MS and NMR spectroscopic data. Nebulosins feature an unprecedented highly substituted thiolane ring leading to up to four contiguous chiral centers. The relative configurations were assigned through a combination of NOESY analysis, spin−spin coupling constant analysis, and NMR chemical shifts measurements, while the absolute configurations were determined by comparison between experimental and theoretical ECD spectra. This family of natural product exhibits promising antioxidant activities in both ORAC and ROS assays.

Marine natural products

“…A series of 16 thiolanes, nebulosins A–P 1487–1491 , 1492 , 1493–1502 were isolated from a northeastern Atlantic collection of the annelid Eupolymnia nebulosa . 738 Nebulosin F 1492 was the most active when tested in antioxidant assays. The structure of pseudocerosine 1503 , an alkaloid responsible for the blue colour of the marginations of the flatworm Pseudoceros indicus , has been revised from an azepinoindole to being a new example of the classical pyridoacridine family.…”

“…A series of 16 thiolanes, nebulosins A-P 1487-1491, 1492, 1493-1502 were isolated from a northeastern Atlantic collection of the annelid Eupolymnia nebulosa. 738 Optimisation of arenicin-3, an amphipathic antimicrobial peptide originally isolated from the worm Arenicola marina, led to the identication of a more potent analogue with signicantly reduced cytotoxicity. 740 Replacement of the intramolecular disulde bond present in arenicin-1 with alanine residues afforded an analogue that retained a b-hairpin structure, exhibited similar levels of antimicrobial activity to arenicin-1 and -2, with slightly weaker haemolytic activity and retained the ability to modulate the complement system.…”

Novel Natural Compounds and Their Anatomical Distribution in the Stinging Fireworm Hermodice carunculata (Annelida)

“…Chemicals including halogenated aromatics, proteins, amino acids and lumazine derivatives were mostly found in the families Sabellidae, Terebellidae, Glyceridae, and Nereididae [10]. Furthermore, "thelepamide" and "nebulosin" have recently been isolated and structurally characterized from Thelepus crispus and Eupolymnia nebulosa respectively [11,12], but chemical defenses from mobile polychaetes remain largely unexplored, and their ecological role has yet to be demonstrated [13,14].…”

Progress on Biological Activity Study and Enantioselective Synthesis of Sulfoxides

“…反应展示了优异的立体控制能力. 值得一提的是, 某些 天然产物 6～8 [12][13][14][15] 中也存在亚磺酰基(图 1b), 如鹅膏蕈 碱 8 [16][17][18] , 它是一种二环八肽, 具有高致死毒性(LD 50 ＝ 50 ～100 μg/kg), 是 RNA 聚合酶 II 的高选择性变构抑制 剂. 此外, 亚磺酰基是羰基的生物等排体 [19] , 在药物结 构设计和改造中也有着广泛的应用, 例如可用于提高药 物分子的水溶性, 影响药物代谢动力学性质, 增强药物 与靶标蛋白的相互结合能力等.…”

“…此外, 亚磺酰基是羰基的生物等排体 [19] , 在药物结 构设计和改造中也有着广泛的应用, 例如可用于提高药 物分子的水溶性, 影响药物代谢动力学性质, 增强药物 与靶标蛋白的相互结合能力等. 1 [1] 2 [2] 3 [3] 4 [4] 5 [5] 6 [12] 7 [14] R [16][17][18] -amanitin 另外, 研究发现, 兰索拉唑 13 及其衍生物与可能导 致阿尔兹海默症等神经退行性疾病的 Tau 神经原纤维缠 结(Neurofibrillary tangles, NFTs), 具有较高的体外亲合 力(IC 50 : 10 -8 ～10 -10 mol/L) [20] . 因此, [ 18 化为较为稳定的阿焦烯(Ajoene, 18)以及其它有机硫化 物(Scheme 2) [21] .…”