Isolation and structure elucidation of new alkaloids from the bryozoan Flustra foliacea

Flustra folicea is an abundant bryozoan in various parts of the North Sea [1].Chemical investigations of the F. foliaca have resulted in a number of unique brominated pyrrolo[2,3-b]indole alkaloids with isoprenyl substituents at various positions. These alkaloids have been shown to have antibacterial [1], nonspecific voltage-sensitive potassium channel blocking [2] and subtype-specific nicotinic acetylcholine receptor blocking activities [3].

The aim of the study was to perform a chemical investigation of the secondary metabolites of F. folicea collected in Icelandic waters using UPLC-qTOF MS/MS analysis, followed by isolation and structure elucidation of new compounds. Dichloromethane:methanol extract of the bryozoan was prepared and the profile of secondary metabolites analysed by UPLC-qTOF-MS/MS and MassLynx. The data indicated the presence of both previously known as well as new compounds. Therefore, the extract was further separated into fractions using various chromatographic methods (e.g. CC, VLC, SPE and preparative HPLC) followed by TLC, ¹H-NMR and UPLC-MS/MS. Structure elucidation was established on the basis of extensive spectroscopic analysis (NMR, MS, UV, and IR). The stereochemistry of the new compounds was determined by NOESY, proton-proton NMR coupling constants, and CD spectra.

In addition to previously known compounds, this study revealed nine new brominated alkaloids, including one rearranged prenylated oxindole alkaloid (1), two prenylated oxindole alkaloids (2-3), and six prenylated pyrrolo[2,3-b]indole- triatomic heterocyclic alkaloids (4-9) and two new imidazole alkaloids (10-11).

The new F. foliacea alkaloids will be virtually screened for activity using an in silico α7 nAChR model and positive hits subsequently tested in vitro for nAChR potentiation.

Acknowledgements: Doctoral grant from the University of Iceland Research Fund.

Keywords: Flustra folicea, bryozoan, brominated alkaloids, imidazole alkaloids.

References:

[1] Peters L, Konig GM, Terlau H, Wright AD. Four new bromo-tryptamine derivatives from the marine bryozoan Flustra foliacea. J Nat Prod 2002; 65: 1633 – 1637

[2] Hodgson JW, Mitchell MO, Thomas ML, Waters KF, Powell D. Deoxypseudophrynaminol: a novel antibacterial alkaloid. Bioorg Med Chem Lett 1995; 5: 2527 – 2528

[3] Peters L, Wright AD, Kehraus S, Gündisch D, Tilotta MC, König GM. Prenylated indole alkaloids from Flustra foliacea with subtype specific binding on NAChRs. Planta Med. 2004; 70: 883 – 886