Semi-Synthesis of C-Ring Cyclopropyl Analogues of Fraxinellone and Their Insecticidal Activity Against Mythimna separata Walker

Abstract

Fraxinellone (1) is a naturally occurring degraded limonoid isolated from Meliaceae and Rutaceae plants. As a potential natural-product-based insecticidal agent, fraxinellone has been structurally modified to improve its activity. Furan ring of fraxinellone is critical in exhibiting its insecticidal activity, but with few modifications. Herein, C-ring-modified cyclopropyl analogues were semi-synthesized by Rh(II)-catalyzed cyclopropanation. The structures of the target compounds were well characterized by NMR and HRMS. The precise three-dimensional structural information of 3a was established by X-ray crystallography. Their insecticidal activity was evaluated against Mythimna separata Walker by a leaf-dipping method. Compound 3c exhibited stronger insecticidal activity than 1 and toosendanin against M. separata with teratogenic symptoms during the different periods, implying that cyclopropanation of the furan ring could strengthen the insecticidal activity of fraxinellone.

Various Biomimetics as Antifungals

“…Natural limonoid derivatives with antifungal activity can be isolated from plant sources and used against pathogenic fungus Cladosporium cucumerinum to reduce the rate of fungal growth [117]. Fraxinellone is the most effective antifungal compound from this group [118], however, this compound and many other lemonoid derivatives can be obtained in a semy-synthetic or synthetic process [111,119]. The synthesis of potential antifungals representing biomimetics of natural limonoids bases on natural enzyme-catalyzed conversion of squalene to lanosterol with participation of oxidosqualene cyclase and squalene epoxidase (monooxidase).…”

Research progress of meliaceous limonoids from 2011 to 2021

“…In order to obtain a large number of derivatives with insecticidal activity, the researchers modied the furan ring and the A ring of fraxinellone. [467][468][469][470][471][472][473][474] Among the derivatives modied by the furan ring, the activity of the derivatives containing the N-phenylpyrazole or N-(1,3-thiazol-2-yl)carboxamides moiety is obviously better than that containing ether, ester, oxime ester, and sulfonate ester, and the introduction of N-(1,3-thiazol-2-yl) carboxamides at the C-2 0 position of fraxinellone was more benecial for the improvement of the insecticidal activity than at C-5 0 . 473 The modication of the A ring of fraxinellone is mainly to hydroxylate C-4 and C-10, and then introduce fragments such as hydrazone, ester, and N-phenylpyrazole.…”

Insights into the Mechanism of Action of the Degraded Limonoid Prieurianin

“…This compound displays marked insecticidal and anticancer activities, linked to its anti-inflammatory and immuno-modulatory properties [22]. Fraxinellone (4) and congeners (e.g., fraxinellonone and isofraxinellone) have led to the synthesis of derivatives and novel insecticide candidates [23][24][25]. There are also fragmented limonoids, often called degraded limonoids, corresponding to smaller products with ring openings associated with the loss of a skeletal fragment [20].…”

“…This compound displays marked insecticidal and anticancer activities, linked to its anti-inflammatory and immuno-modulatory properties [22]. Fraxinellone (4) and congeners (e.g., fraxinellonone and isofraxinellone) have led to the synthesis of derivatives and novel insecticide candidates [23][24][25].…”