Synthesis and Herbicidal Activities of Enantiopure Methiozolins

Abstract

It is well known that the worldwide demands for crops and biomass exceed their supply due to the rapid growth of world population, limitation of cultivation areas, global warming, climate change and subsequent lack of water supply. Herbicides for weeds control have played an important role in promoting productivity of crops yields and biomass. 1 Even though a number of herbicides have been developed for weeds control, more eco-friendly new herbicides having new modes of action are needed because of the environmental safety issues and occurrence of resistant weeds. 2,3 Recently, a new isoxazoline herbicide methiozolin possessing thiophene ring for the control of grass weeds in turf grass has been commercialized. 4,5 Methiozolin shows not only excellent herbicidal efficacy toward several grass weeds in turf grass but also favorable toxicological and environmental profiles. Methiozolin has one chiral center in isoxazoline ring. Up to now, methiozolin has been developed as a racemate.However, it was reported that, in many cases, big differences in biological activities between enantiomers of chiral agrochemicals have been observed. 6-8 In addition, success stories for the commercialization of chiral agrochemicals such as (S)-metolachlor 9 and mefenoxam 10 as a single isomer by Syngenta prompted us to investigate herbicidal activities of each enantiomer of methiozolin. In our previous paper, 11 the absolute stereochemistry of one enantiopure intermediate with posititive value of specific optical rotation, which is the key intermediate for synthesis of optically active methiozolin, was determined by single crystal X-ray diffraction analysis after prep-HPLC separation with chiral stationary phase [(R,R)-WHELK-O1 column] using [5-methyl-3-(3-methylthiophen-2-yl)-4,5-dihydroisoxazol-5-yl]methanol as the racemic mixture. Herein, we want to describe synthesis of enantiopure methiozolins and compare herbicidal activities between optical isomers on some grass weeds under a greenhouse condition.Key intermediates (S)-3 and (R)-3 for enantiopure methiozolins could be obtained by chiral separation of a racemic

Methiozolin Efficacy, Absorption, and Fate in Six Cool‐Season Grasses

“…Turfgrass growth inhibition from methiozolin is consistent with previous research on creeping bentgrass but responses of other cool‐season species have received limited investigation. Annual bluegrass growth suppression has been noted with both preemergence and postemergence methiozolin applications and is attributed to efficacy for control (Flessner et al, 2013; McCullough et al, 2013; Nam et al, 2012). In growth chamber experiments, creeping bentgrass injury was exacerbated when the temperature was reduced from 30 to 10°C but turf had less injury than annual bluegrass at all temperatures (McCullough et al, 2013).…”

Methiozolin sorption and mobility in sand-based root zones

“…10 However, the exact site or enzyme of inhibition is believed to be different from that of other herbicides inhibiting cell wall biosynthesis. 1,10,11 Methiozolin is absorbed by the roots and foliage of annual bluegrass. 2,3,8 Root exposure and subsequent absorption is required for POST control.…”

“…Another reported mode of action for methiozolin is cell wall biosynthesis inhibition, which was evaluated using maize ( Zea mays L.) . However, the exact site or enzyme of inhibition is believed to be different from that of other herbicides inhibiting cell wall biosynthesis , …”

Methiozolin Absorption and Translocation in Annual Bluegrass (Poa annua)

“…], and annual bluegrass (Brosnan et al 2013;Han and Kaminski 2011;Hwang and Koo 2009;Hwang et al 2005;McCullough and Gómez de Barreda 2012;McNulty and Askew 2011;Nam et al 2012;Norsworthy et al 2011). Methiozolin reportedly controls annual bluegrass PRE and POST through multiple and timely applications (Haguewood et al 2012;Kaminski 2011, 2012;Hoyle et al 2012;Hwang and Koo 2009;McNulty and Askew 2011;Nam et al 2012;Trappe et al 2012). Methiozolin has been reported to inhibit tyrosine aminotransferase (TAT); this inhibition blocks the production of plastoquinone and tocopherol, both of which are important in membrane protection to oxidative stresses (Grossmann et al 2012).…”

“…Another proposed mode-of-action for methiozolin is cell wall biosynthesis inhibition, which was established using maize (Zea mays L.) (Lee et al 2007). However, the exact site/ enzyme of inhibition is believed to be different from that of other cell wall biosynthesis-inhibiting herbicides (Hwang et al 2005;Lee et al 2007;McNulty and Askew 2011;Nam et al 2012).…”