Structure–activity relationships of N- and S-analogs of the seed germination inhibitor (3,4,5-trimethylfuran-2(5H)-one) for mode of action elucidation

Abstract

Smoke-derived butenolides are important germination signaling molecules which may be useful in promoting or controlling germination in agriculture and horticulture. The butenolide 3,4,5-trimethylfuran-2(5H)-one (trimethylbutenolide; TMB) was previously isolated from plant-derived smoke and was found to significantly reduce the germination stimulatory activity of the highly active germination promoter, 3-methyl-2H-furo[2,3-c]pyran-2-one (karrikinolide; KAR1), another smoke-derived butenolide, when applied together. In this study, the germination inhibitory activity of eight N-analogs and one S-analog of TMB, modified in position 1 were evaluated. All synthesized analogs significantly reduced the germination of ‘Grand Rapids’ lettuce (Lactuca sativa) seeds compared to the respective controls, when applied at 1000 µM alone, or in combination with 0.01 µM KAR1. The S-analog was the most active of the test analogs in this study, with inhibitory activity ranging from 10 to 1000 µM. This was the only compound with activity similar to that of TMB. Thus, these results indicate that N-alkylation of the lactam ring reduces its germination inhibitory activity, while the activity of the S-analog is comparable to TMB. This provides valuable information toward understanding the mode of action of these compounds in regulating germination and for the design of related synthetic compounds with potential use in agriculture or horticulture.