Semi-synthesis and insecticidal activity of spinetoram J and its D-forosamine replacement analogues

Abstract

Spinetoram, a mixture of spinetoram J (XDE-175-J, major component) and spinetoram L (XDE-175-L), is a new kind of fermentation-derived insecticide with a broad range of action against many insect pests, especially Cydia pomonella, Leaf miner and Thrips. Similar to spinosad, spinetoram is friendly to the environment, and non-toxic to animals and human beings. Therefore, spinetoram has been widely applied in pest control and grain storage. In a previous study, we had reported a semi-synthesis of spinetoram J. However, in that synthesis, there were more experimental steps, and the operations were troublesome. So an improved synthesis based on a self-protection strategy was designed and discussed. In this work, 3-O-ethyl-2,4-di-O-methylrhamnose was used as both the reaction substrate of C9–OH and the protecting group of C17–OH. The number of synthetic steps and costs were significantly reduced. In addition, a variety of D-forosamine replacement analogues of spinetoram J were synthesized based on the improved semi-synthesis, and their insecticidal activities were evaluated against third-instar larvae of Plutella xylostella. Although none of the analogues were as potent as spinetoram, a few of the analogues have only a 20–40 times lower activity than spinetoram. In particular, one of these analogues was approximately as active as spinosad. This study highlights the possibility of developing new insecticidal chemistries by replacing sugars on natural products with other groups, and the improved semi-synthesis will be helpful for further researches on spinetoram.

Effect of insecticide molecules on fall armyworm Spodoptera frugiperda (J. E. Smith) on maize under field conditions

“…Spinoteram is friendly to the environment and nontoxic to animals and human beings. Therefore it has been widely used in pest control and grain storage (Zhang et al, 2018). nimbecidine 0.03% @ 3 ml/l, Bacillus thuringiensis var.…”

Hormetic and transgenerational effects in spotted-wing Drosophila (Diptera: Drosophilidae) in response to three commonly-used insecticides

“…The genetic variability hypothesis is bolstered by the fact that the discrepancy between the initial dose-response curves and experimental results were similar for the insecticides with the same mode of action. Zeta-cypermethrin and pyrethrin are both sodium channel modulators [ 108 , 109 ], while spinetoram is a spinosad that acts on GABA-gated chloride channels [ 110 , 111 ]. The sex-specific differences in survivorship, on the other hand, seem to be impacted by the intensity of the insecticide, as differences between male and female flies were greater in the zeta-cypermethrin and spinetoram treatments, both synthetic insecticides, than the pyrethrin treatment, an organic insecticide.…”

The spinosyns, spinosad, spinetoram, and synthetic spinosyn mimics ‐ discovery, exploration, and evolution of a natural product chemistry and the impact of computational tools

“…While much of the semi‐synthetic modifications of the spinosyns were focused on small changes to the spinosyn structure, more substantial modifications in the form of replacing the spinosyn the forosamine and rhamnose sugars has also been also explored. Non‐sugar forosamine replacements were generally less active than corresponding forosamine analogs, 33,49 as were most alternative sugars 50 . However, minor spinosyn factors possessing naturally occurring alternative sugars (e.g., D ‐amicetose, methyl‐oleandrose), were in some cases as insecticidally active as the corresponding forosamine analogs 16,18 .…”