Synthesis of Novel Spinosyn A Analogues by Pd-Mediated Transformations

The concept of modern crop protection demands for a continuous supply of new or modified established pesticides to avoid the development of serious resistances. Recent reports on the insecticidal spinosyns 1 and 2 show that also this class of pest managing agents is increasingly exposed to the formation of resistances. The synthesis of new derivatives is therefore highly desirable. We describe in this paper a convergent approach towards novel enantiopure spinosyn A analogues of type 3, which is based on investigations of structure–activity relationships and employs a twofold Heck reaction as key step for the preparation of the tricyclic backbone assembly. Resistance management: In the last years several signs of resistance to the spinosyns, worldwide used important insecticides, have occurred. Therefore a convergent approach to novel enantiopure spinosyn A analogues, such as depicted, on the basis of investigations of structure–activity relationships was developed. The key step is a twofold Heck reaction followed by an Evans aldol addition, a Grignard coupling and a macrolactonization.