The insecticidal activity of derivatives of the ionophore X-206

Abstract

The naturally‐occurring ionophore X206, originally isolated for its antibacterial activity, also exhibits broad insecticidal and acaricidal activity. This summary reports structure/activity studies with X206 and 34 derivatives as well as mode of action studies. Although many compounds showed promising insecticidal activity, it was only of a contact activity nature; furthermore, the acute LD50 of the compounds in rats precluded further development of these compounds. © 1999 Society of Chemical Industry

Use of the Potassium Ion as a Template for the Selective Derivatization of the Antibiotic X-206

“…A useful intermediate ( 2 ), protected by hydrogenolytically cleavable groups, was used to synthesize a number of C(22) derivatives. These compounds turned out to be promising insecticides, particularly the C(22) esters, some of which were much better insecticides than X-206 itself . As greater numbers and larger amounts of derivatives were required, a simpler route to their preparation was sought.…”

“…These compounds turned out to be promising insecticides, particularly the C(22) esters, some of which were much better insecticides than X-206 itself. 13 As greater numbers and larger amounts of derivatives were required, a simpler route to their preparation was sought. This goal was achieved by exploiting the templating effect of potassium ions to prepare the desired C(22) esters in a single step as described below.…”

“…The determination of C(22) in X-206 as a position that can be modified without loss of activity is important and useful for a number of reasons. First, it led to the synthesis of compounds with greatly improved insecticidal activity, although sadly their toxicological profile prohibited practical use . Furthermore, with this methodology, a functionally active ionophoric X-206 may now be covalently attached to fluorescent or radioactive markers, photoaffinity labels, proteins, and solid phases.…”

“…First, it led to the synthesis of compounds with greatly improved insecticidal activity, although sadly their toxicological profile prohibited practical use. 13 Furthermore, with this methodology, a functionally active ionophoric X-206 may now be covalently attached to fluorescent or radioactive markers, photoaffinity labels, proteins, and solid phases. Because of the large number of functional groups in ionophores, the means of reacting selectively and extraperipherally is all important.…”

“…We therefore chose it as a position suitable for derivatization. Indeed, it transpired that derivatives at C(22) bound potassium well and were interesting insecticides, whereas derivatives at C(1), C(9), or C(34) were either very weak or inactive, either as insecticides or ionophores 1 X-ray structure of X-206 sodium salt. …”