Catalyst Development for the Synthesis of Ozonides and Tetraoxanes Under Heterogeneous Conditions: Disclosure of an Unprecedented Class of Fungicides for Agricultural Application

Abstract

The catalyst H3+xPMo12−x+6Mox+5O40 supported on SiO2 was developed for peroxidation of 1,3‐ and 1,5‐diketones with hydrogen peroxide with the formation of bridged 1,2,4,5‐tetraoxanes and bridged 1,2,4‐trioxolanes (ozonides) with high yield based on isolated products (up to 86 and 90 %, respectively) under heterogeneous conditions. Synthesis of peroxides under heterogeneous conditions is a rare process and represents a challenge for this field of chemistry, because peroxides tend to decompose on the surface of a catalyst . A new class of antifungal agents for crop protection, that is, cyclic peroxides: bridged 1,2,4,5‐tetraoxanes and bridged ozonides, was discovered. Some ozonides and tetraoxanes exhibit a very high antifungal activity and are superior to commercial fungicides, such as Triadimefon and Kresoxim‐methyl. It is important to note that none of the fungicides used in agricultural chemistry contains a peroxide fragment.

Cyclic Synthetic Peroxides Inhibit Growth of Entomopathogenic Fungus Ascosphaera apis without Toxic Effect on Bumblebees

“…The objects of the study were adult male bumblebees Bombus terrestris L. (more than 3 days after hatching from pupae), as well as bumblebee larvae provided by the Technology of Bumblebee Rearing Ltd. (Voronezh, Russia). Ozonide 1, bridged 1,2,4,5-tetraoxanes 2-6 [25], and tricyclic monoperoxides 7,8 [55] were synthesized in accordance with previously reported procedures. Physical data and description of 1 H and 13 C-NMR spectra of peroxides 1-8 see in the Supplementary Materials.…”

“…In 2015, the Nobel Prize in Medicine was awarded to Youyou Tu for the discovery and development of Artemisinin, a natural peroxide antimalarial drug [24]. Recently, we have discovered a new class of antifungal agents for crop protection, cyclic peroxides: bridged 1,2,4,5-tetraoxanes and bridged ozonides [25]. These peroxides possess a high fungicidal activity against a broad spectrum of phytopathogenic fungi.…”

Development of Biodegradable Delivery Systems Containing Novel 1,2,4-Trioxolane Based on Bacterial Polyhydroxyalkanoates

“…The discovery of the natural peroxide artemisinin [1][2][3], which has antimalarial properties, was the beginning of the development of biologically active peroxides (Figure 1). It has been found that cyclic peroxides have antimalarial [4][5][6][7][8][9][10][11][12], antiparasitic [13][14][15][16][17][18][19], anticancer [20][21][22][23][24][25][26][27][28][29][30][31], antiviral [32][33][34], and fungicidal [18,35,36] activities. On the basis of the fully synthetic peroxide arterolane, which contains a 1,2,4-trioxolane (ozonide) fragment, has been created an antimalarial drug of the latest generation-Synriam [37].…”

“…The absorption maxima of the substance are in the UV region (268 and 276.5 nm). Since ozonides related to OZ exhibit anticancer [25][26][27], antiparasitic [57], and fungicidal activity [36], PHA-microparticles containing OZ might be potentially used for cancer treatment along with other known drug delivery systems based, for example, on lipid nanovesicles [58], leukocyte-mimicking nanovesicles [59], and immunoliposomes [60].…”

Application of BF3·Et2O in the synthesis of cyclic organic peroxides (microreview)

“…Medicinal chemists and pharmacologists recognize cyclic peroxides as an uncharted chemical space for drug design. Cyclic peroxides exhibit antiparasitic, 1 anticancer, 2 antifungal, 3 and antiviral 4 activities. Ethanolic extract of Artemisia annua L. possesses antiviral activity against SARS-associated coronavirus.…”