Natural ten-membered lactones: sources, structural diversity, biological activity, and intriguing future

Abstract

Ten-membered lactones (TMLs) are an interesting and diverse group of natural polyketides that are abundant in fungi and, to a lesser extent, in bacteria, marine organisms, and insects.

Structure–Activity Relationships of Natural C-9-Methyl-Substituted 10-Membered Lactones and Their Semisynthetic Derivatives

“…The 13 C NMR spectrum (Table ) shows 10 carbon signals: one lactone carbonyl carbon (C-1 at δ 169.3) and one keto group (C-4 at δ 207.9), three methylene carbons (C-2, C-3, and C-5 at δ 30.7, 35.9, and 50.1), four oxymethine carbons (C-6, C-7, C-8, and C-9 at δ 68.6, 62.4, 59.2, and 67.7), and one methyl carbon (Me-10 at δ 16.8). The analysis of these results and a recently published review led us to conclude that compound 1 is a TML structurally related to decarestrictine B . The 1 H NMR (Table ) showed signals of three pairs of aliphatic methylene protons at δ H 2.95 (1H, ddd, 17.4, 12.6, 4.8, H-2a) and δ H 2.52 (1H, ddd, 17.4, 4.3, 3.5, H-2b), δ H 3.11 (1H, ddd, 15.7, 12.4, 4.5, H-3a) and δ H 2.23 (1H, ddd, 15.8, 4.6, 3.4, H-3b), δ H 3.00 (1H, dd, 11.7, 3.5, H-5a) and δ H 2.67 (1H, t, 11.3, H-5b); four oxymethine protons at δ H 4.29 (1H, ddd, 10.9, 8.6, 3.5, H-6), δ H 3.09 (1H, dd, 8.6, 4.2, H-7), δ H 3.41 (1H, dd, 5.6, 4.3, H-8), and δ H 5.35 (1H, dq, 6.7, 5.8, H-9); and the terminal methyl group at δ H 1.29 (3H, d, 6.7, CH 3 -10).…”

“…In contrast to previous works devoted to C-9 propyl-substituted TMLs, the aim of this study was to analyze the SAR of natural and semisynthetic TMLs with a methyl group at C-9 and a highly substituted lactone ring. Most TMLs described in the literature belong to this group; they are highly diverse in their oxygenation patterns. However, they are much less studied in terms of their phytotoxic activity than C-9 propyl-substituted TMLs.…”

“…This multitarget bioassay approach shed light on little-studied types of biological activity of TMLs. 2…”

“…Fungal 10-membered lactones (TMLs) represent an interesting and structurally diverse group of secondary metabolites with potent biological activity. , Several TMLs (putaminoxins, herbarumins, stagonolides, and others) are known as promising candidates for the development of nature-derived herbicides. − Nevertheless, the rational optimization of their structures for use as plant protection products is complicated by poorly explored relationships between the structure and herbicidal activity.…”

“…We performed a panel of bioassays, including not only the target activity assessment (phytotoxic) but also the off-target toxicity evaluation (antimicrobial, entomotoxic, cytotoxic). This multitarget bioassay approach shed light on little-studied types of biological activity of TMLs …”