Talarolides Revisited: Cyclic Heptapeptides from an Australian Marine Tunicate-Associated Fungus, Talaromyces sp. CMB-TU011

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 (2–4). 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 2–4. Consideration of diagnostic ROESY correlations for the hydroxamates 1 and 3–4, 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.

Jugiones A–D: Antibacterial Xanthone–Anthraquinone Heterodimers from Australian Soil-Derived Penicillium shearii CMB-STF067

“…Interestingly, a 2016 [12] re-isolation of 5 together with its isomer engyodontochone B (6) from a Croatian marine sponge-derived fungus, Engyodontium album LF069, employed ROESY and ECD correlations to assign absolute configurations to both 5 and 6 (Figure 3). Also noteworthy are the biosynthetically related xanthoquinodins B10 (7) and B11 (8), first reported in 2020 [13] from a Nepalese soil-derived fungus, Jugulospora vestita CBS 135.91, and assigned structures and absolute configurations based on spectroscopic and ECD analysis (Figure 3). Careful consideration of the spectroscopic data for 5-7, which collectively encompass the full array of C-24/C-25 stereoisomers, reveals useful empirical rules.…”

“…temperature, aeration…) [2][3][4], we employed a miniaturized 24-well plate approach to cultivation profiling known in lab as the MATRIX [5]. When integrated with UPLC-DAD and GNPS molecular networking, MATRIX analyses can be particularly effective and have proved pivotal to our prior discovery and reporting of many new natural-product structure classes (e.g., noonindoles [6], chrysosporazines [7], talarolides [8] and terreusides [9]). In this study, we employed both the standard MATRIX [5] and newly developed grain/pulse and cereal MATRIX [9] variations to probe the metabolite production capabilities of CMB-STF067.…”