Summary
X-ray database searches and theoretical potential-energy calculations indicate that the acid moieties of pyrethroid cyclopropanecarboxylate esters adopt a well-defined, relatively inflexible conformation. In contrast, the alcohol moieties can exist in many low-energy geometries. One of the least conformationally flexible pyrethroid alcohols is 4-phenylindan-2-ol. The approximate overall conformation adopted at the biological binding site by insecticidal esters of this alcohol can be deduced with reasonable confidence by molecular modelling. Graphics superposition of a variety of pyrethroid acids suggests the existence of a large but rather narrow pocket at the binding site, in which substituents at the 3-position of the cyclopropane ring can be accommodated. This pocket is asymmetric with respect to the plane of the cyclopropane ring, extending further on the side remote from the ester group. The effects of α-substitution on the insecticidal activity of pyrethroid esters may be due to the influence of substituents on the preferred conformations of the molecules. This hypothesis rationalises the paradoxical dependence on absolute stereochemistry of the activities of various allylbenzyl and cinnamyl alcohol derivatives.
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Supplementary material available from the authors: Five pages with Cartesian coordinates of hypothesised active conformations of compounds 1, 4, 7, 22–27, 34, 42 and 45.
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Mullaley, A., Taylor, R. Conformational properties of pyrethroids. J Computer-Aided Mol Des 8, 135–152 (1994). https://doi.org/10.1007/BF00119864
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DOI: https://doi.org/10.1007/BF00119864