Chemistry of Herbarumin I, Stagonolide A, and Structurally Related Phytotoxic Ten-Membered Lactones: Oxidative Cleavage, Stereospecific Epoxidation, Transannulation, and Dimerization

Chemistry of Herbarumin I, Stagonolide A, and Structurally Related Phytotoxic Ten-Membered Lactones: Oxidative Cleavage, Stereospecific Epoxidation, Transannulation, and Dimerization Full article

Journal

Journal of Natural Products
ISSN: 0163-3864 , E-ISSN: 1520-6025

Output data

Year: 2026, DOI: 10.1021/acs.jnatprod.5c01426

Authors

Fedorov Anatoly ¹ , Alekseeva Alena ² , Dalinova Anna ² , Kretov Daniil ³ , Radiupov Valentin ⁴ , Slukin Anton ⁴ , Khrustalev Victor N. ^5,6 , Smirnov Sergey N. ⁴ , Sikalov Alexander ⁷ , Zaichenko Aleksandr ⁸ , Berestetskiy Alexander ²

Affiliations

1	Independent Researcher
2	All-Russian Institute of Plant Protection, Podbelskogo Street, 3, Pushkin, Saint Petersburg 196608, Russian Federation
3	Peter the Great St.Petersburg Polytechnic University, aint Petersburg 195251, Russian Federation
4	Saint Petersburg State University, Universitetsky Av. 26, Saint Petersburg 198504, Russian Federation
5	N. D. Zelinsky Institute of Organic Chemistry of Russian Academy of Sciences, Leninsky Prospect, 47, Moscow 119991, Russian Federation
6	Peoples’ Friendship University of Russia (RUDN University), 6 Miklukho-Maklay Street, Moscow 117198, Russian Federation
7	University of Chicago, 929 E 57th Street, Chicago 60637, Illinois, United States
8	Academia Libera, Buffalo 14226, New York, United States

Ten-membered lactones (TMLs) produced by phytopathogenic fungi are considered model compounds for the development of nature-inspired agrochemicals with novel mechanisms of action. Despite their structural simplicity, TMLs display a broad range of biological activities. Although total synthesis methods for many TMLs have been developed, systematic data on their chemical properties remain highly limited. To address this gap, we investigated the reactivity of herbarumin I, 2-epi-herbarumin II, stagonolides J and K, pinolidoxin, and their C-7 oxidized analogs in oxidation, hydrogenation, and isomerization reactions. We demonstrate that their spatially constrained architecture and functional group topology promote distinctive and reproducible reactivity patterns, including stereospecific epoxidation at the C5–C6 bond, mild oxidative cleavage at C7–C8, Pd/Pt-catalyzed allylic transposition, transannulation to chromone derivatives, and base-induced dimerization into fused tetrahydrofuran scaffolds. As a result, 31 new compounds were synthesized, three new reactions were discovered with mechanistic insights provided, and the absolute configuration was established for stagonolide J and stagochromene A and revised for 5,6-epoxypinolidoxin. Preliminary conclusions were drawn about the chemical lability of unsaturated C7-keto derivatives of TMLs in protic media. Such mapping of structure–reactivity relationships within this subclass of TMLs provides a foundation for future semisynthetic derivatization, chemical stability assessment, and rational expansion of biologically relevant scaffolds.

Fedorov A. , Alekseeva A. , Dalinova A. , Kretov D. , Radiupov V. , Slukin A. , Khrustalev V.N. , Smirnov S.N. , Sikalov A. , Zaichenko A. , Berestetskiy A.
Chemistry of Herbarumin I, Stagonolide A, and Structurally Related Phytotoxic Ten-Membered Lactones: Oxidative Cleavage, Stereospecific Epoxidation, Transannulation, and Dimerization
Journal of Natural Products. 2026. DOI: 10.1021/acs.jnatprod.5c01426 WOS OpenAlex

Submitted:	Nov 13, 2025
Published print:	Jan 29, 2026

Web of science:	WOS:001674290200001
OpenAlex:	W7126120736

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