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Keywords = hydroxamate H-bond bridge

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9 pages, 2040 KiB  
Article
Total Synthesis of Talarolide A and atrop-Talarolide A: Hydroxamate H-Bond Bridge Stabilization of Cyclic Peptide Conformers Invokes Non-Canonical Atropisomerism
by Waleed M. Hussein, Yuxuan Zhu, Angela A. Salim and Robert J. Capon
Mar. Drugs 2024, 22(10), 454; https://doi.org/10.3390/md22100454 - 3 Oct 2024
Cited by 1 | Viewed by 1800
Abstract
The first total synthesis of the Australian marine tunicate fungus-derived cyclic peptide talarolide A (1) has confirmed the structure previously proposed on the basis of spectroscopic and chemical analyses and re-affirmed the importance of the unique hydroxamate H-bond bridge in ring [...] Read more.
The first total synthesis of the Australian marine tunicate fungus-derived cyclic peptide talarolide A (1) has confirmed the structure previously proposed on the basis of spectroscopic and chemical analyses and re-affirmed the importance of the unique hydroxamate H-bond bridge in ring conformer stabilization. The unexpected co-synthesis of atrop-talarolide A (8) revealed, for the first time, that hydroxamate H-bond bridging in the talarolide framework invokes non-canonical atropisomerism and that talarolides A (1), C (3), and D (4) all exist naturally as atropisomers. These discoveries raise the intriguing prospect that comparable functionalisation of other cyclic peptides, including those with commercial value, could provide ready access to new “unnatural atropisomeric” chemical space, with new and/or improved chemical and biological properties. Full article
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17 pages, 5543 KiB  
Article
Talarolides Revisited: Cyclic Heptapeptides from an Australian Marine Tunicate-Associated Fungus, Talaromyces sp. CMB-TU011
by Angela A. Salim, Waleed M. Hussein, Pradeep Dewapriya, Huy N. Hoang, Yahao Zhou, Kaumadi Samarasekera, Zeinab G. Khalil, David P. Fairlie and Robert J. Capon
Mar. Drugs 2023, 21(9), 487; https://doi.org/10.3390/md21090487 - 11 Sep 2023
Cited by 5 | Viewed by 3743
Abstract
Application of a miniaturized 24-well plate system for cultivation profiling (MATRIX) permitted optimization of the cultivation conditions for the marine-derived fungus Talaromyces sp. CMB-TU011, facilitating access to the rare cycloheptapeptide talarolide A (1) along with three new analogues, B–D (2 [...] Read more.
Application of a miniaturized 24-well plate system for cultivation profiling (MATRIX) permitted optimization of the cultivation conditions for the marine-derived fungus Talaromyces sp. CMB-TU011, facilitating access to the rare cycloheptapeptide talarolide A (1) along with three new analogues, B–D (24). Detailed spectroscopic analysis supported by Marfey’s analysis methodology was refined to resolve N-Me-l-Ala from N-Me-d-Ala, l-allo-Ile from l-Ile and l-Leu, and partial and total syntheses of 2, and permitted unambiguous assignment of structures for 1 (revised) and 24. Consideration of diagnostic ROESY correlations for the hydroxamates 1 and 34, and a calculated solution structure for 1, revealed how cross-ring H-bonding to the hydroxamate moiety influences (defines/stabilizes) the cyclic peptide conformation. Such knowledge draws attention to the prospect that hydroxamates may be used as molecular bridges to access new cyclic peptide conformations, offering the prospect of new biological properties, including enhanced oral bioavailability. Full article
(This article belongs to the Special Issue Diversity of Marine Fungi as a Source of Bioactive Natural Products)
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