Synthesis of Novel Spinosyn A Analogues by Pd‐Mediated Transformations

Abstract

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.

The spinosyn family of insecticides: realizing the potential of natural products research

“…29,30 In addition, studies analyzing methodology for the synthesis of both the natural product and certain analogs have been conducted. [31][32][33][34] FERMENTATION-DERIVED ANALOGS Numerous structurally related compounds from various spinosyn fermentations have now been isolated and identified. Their structures fall into several general categories of single-type changes in the aglycone or saccharides of spinosyn A (Figure 2).…”

Pr(OTf)3-promoted Chichibabin pyridine synthesis of isodesmosine in H2O/MeOH

“…Protection of the carboxyl group as the corresponding tert-butyl ester was achieved using O-tert-butyl-N,N 0 -diisopropyl isourea, which was freshly prepared from N,N 0 -diisopropylcarbodiimide. 12 Compound 3 and the isourea were reacted in dichloromethane (CH 2 Cl 2 ) at room temperature to give the tert-butyl ester 4 in 98% yield. Subsequent removal of the benzyloxycarbonyl group under Pd/C hydrogenation conditions in MeOH gave the desired amine 5 in 96% yield.…”

Three‐Component Domino Knoevenagel/Hetero‐Diels–Alder Reaction for the Synthesis of the Amino Sugars 2‐Acetoxyforosamine and 2‐Acetoxyossamine – Experimental and Theoretical Results

“…[4a] Following this approach in our attempts to prepare new analogues of spinosyn A (1) [9] to overcome resistance of this highly potent insecticide, we prepared (2R)-2-acetoxyforosamine [8] starting from d-abequose in a lengthy approach. Here we describe a short and highly efficient synthesis of ethyl-2-acetoxyforosamines (21)(22)(23)(24) and the diastereomeric ethyl-2-acetoxyossamine (25) using a three-component domino Knoevenagel/hetero-Diels-Alder reaction with inverse electron demand, employing simple and easily accessible starting materials.…”