The Stereochemical Outcome of Electrophilic Addition Reactions on the 5,6-Double Bond in the Spinosyns

Abstract

The electrophilic addition of reagents to the 5,6-double bond in spinosyn A and spinosyn D systems occurred with high pi-diastereofacial selectivity. Addition occurred preferentially from the beta face of the molecule with selectivities ranging from 5:1 to better than 30:1. Various NMR properties were investigated in order to distinguish the beta and alpha isomers with the help of theoretical models of the products. These NMR properties include a (13)C gamma effect to C-11 and vicinal coupling between H-4 and H-5. To help rationalize the selectivity, computational studies on the transition states for epoxidation were calculated using density functional theory. The results indicate that beta epoxidation is favored and that the geometries of the transition structures are consistent with torsional steering being the source of the selectivity.

Structural Studies of the Spinosyn Rhamnosyltransferase, SpnG

“…The SpnG-TDP and SpnG-AGL structures were solved by molecular replacement using the apo-SpnG structure. The model for AGL was obtained by removing the sugars from the spinosyn A crystal structure (24). The configuration of 12-membered ring was slightly adjusted, using the appropriate regularization parameters within Coot, so that it fit the electron density map (21).…”

“…The model for AGL was obtained by removing the sugars from the spinosyn A crystal structure. 24 The configuration of the 12-membered ring was slightly adjusted, using the appropriate regularization parameters within Coot, so that it fit the electron density map. 21 Site-Directed Mutagenesis.…”

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

“…82,86 Early modifications of the tetracyclic core included several stereoselective reductions and epoxidations of the 5,6-and 13,14-double bonds (see Figure 1). 57,87 However, the 6-methyl group of spinosyn D (2, Figure 1) substantially hindered hydrogenation of its 5,6-double bond. The biological activity of these oxidation and reduction products was usually dependent on the stereochemistry of the reaction products.…”

New trends in pest control: the search for greener insecticides

“…79,87 Much effort has been devoted to the synthesis of the tricyclic nucleus of spinosyns or related structures so as to allow access to pure diastereomeric spinosoids. 88 As the biosynthesis 89,90 of spinosyn A is supposed to involve a transannular Diels-Alder reaction and a ring closure of a macrocyclic pentaene, several synthetic approaches are based on these reactions.…”