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Lookup NU author(s): Dr Kin Lok Ho, Alexandra Longcake, Dr Michael HallORCiD, Professor Mike ProbertORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Wheldone was reported recently as a fungal metabolite isolated from the co-culture of Aspergillus fischeri and Xylaria flabelliformis, and it displayed cytotoxic activity against breast, melanoma, and ovarian cancer cell lines. Initially, its structure was characterized as an unusual 5-methyl-bicyclo[5.4.0]undec-3,5-diene scaffold with a 2‑hydroxy-1-propanone side chain and a 3-(2-(1-hydroxyethyl)-2-methyl-2,5-dihydrofuran-3-yl)acrylic acid moiety. Upon further examination, minor inconsistencies in the data suggested the need for structural revision. Thus, the structure of wheldone has been revisited herein using an orthogonal experimental-computational approach, which combines 1,1-HD-ADEQUATE NMR experiments, DFT-GIAO chemical shift calculations, and single crystal X-ray diffraction (SCXRD) analysis of a semi-synthetic p‑bromobenzylamide derivative, formed via a Steglich-type reaction. The summation of these data, in conjunction with previously reported Mosher’s ester analysis, now permit the unequivocal assignment of both the structure and absolute configuration of the natural product.
Author(s): Rangel-Grimaldo M, Earp CE, Raja HA, Wood JS, Crull EB, Mardiana L, Ho KL, Longcake A, Williamson RT, Palatinus L, Hall MJ, Probert MR, Oberlies NH
Publication type: Article
Publication status: Published
Journal: Journal of Natural Products
Year: 2024
Volume: 87
Issue: 8
Pages: 2095-2100
Print publication date: 23/08/2024
Online publication date: 23/07/2024
Acceptance date: 11/07/2024
Date deposited: 05/08/2024
ISSN (print): 0163-3864
ISSN (electronic): 1520-6025
Publisher: American Chemical Society
URL: https://doi.org/10.1021/acs.jnatprod.4c00649
DOI: 10.1021/acs.jnatprod.4c00649
Data Access Statement: The NMR data for wheldone have been deposited in the Natural Products Magnetic Resonance Database (NP-MRD; www.np_mrd.org) and can be found at NP0021048. Also, CCDC 2330603 contains the supplementary crystallographic data for this paper, and these data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre,12 Union Road, Cambridge CB2 1EZ, UK; fax:+441223336033.
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