The Synthesis Of Spinosad Derivatives

Spinosad compound is a kind of very valuable secondary natural fermentationproducts of actinomycete Saccharopolyspora spinosa. It is a novel macrolide insecticideactive substance. It has many advantages such as high insecticidal activity, wide pesticidalspectrum, low toxicity, easy degradation characteristics, So it has won AmericanPresidential Green Chemistry Challenge award twice. In order to find new broad-spectrumspinosad derivatives, persistent efforts have been paid for the structural modification ofnatural fermentation product of spinosad.Spinosad concludes a5,6,5-tricyclic fused12-membered macrolide lactone ring andC-9and C-17are respectively connected with two different six membered heterocyclicsugars: rhamnose sugar and forosamine sugar. This paper designed and synthesized a seriesof spinosad derivatives by the chemical modification of spinosad A.Spinosad A was firstly hydrolyzed to give17-Pseudoaglycone(I) and Aglycone(II).Then taking the two hydrolysis products as raw materials, a series of C-17single acylatedproducts and C-9, C-17double acylated products were synthesized. The structure ofsynthesized products were characterized by1H NMR、13C NMR、high resolution MS. Thebetter acylation reaction conditions were40°C-60°C, DMAP or NaH as catalyst. Theintroduced groups included acetyl、cyclohexoyl、furoyl、nicotinate、adamantane formyl、Nitrogen containing heterocyclic formyl、trifluoroacetyl. In this paper the biological activityof esterified derivatives were also studied, and the results showed that introduceadamantane formyl and heterocyclic derivatives could improve the insecticidal activity andinsecticide spectrum.By using17-Pseudoaglycone (I) as material, the glycoside modification of spinosadwas also studied. First the reaction of sugar with2,2,2-trifluoro-N-phenylacetimidoylchloride afforded glycosyl donor. Then the glycosyl donor reacted with glycosyl acceptor,17-Pseudoaglycone (I). A series of N-phenyl trifluoroacetimidatest glycosyl donor, theglycoside spinosad derivatives were synthesized.