Synthesis and Herbicidal Activity of Triketone–Quinoline Hybrids as Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors

Abstract

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) is one of the most important targets for herbicide discovery. In the search for new HPPD inhibitors with novel scaffolds, triketone-quinoline hybrids were designed and subsequently optimized on the basis of the structure-activity relationship (SAR) studies. Most of the synthesized compounds displayed potent inhibition of Arabidopsis thaliana HPPD (AtHPPD), and some of them exhibited broad-spectrum and promising herbicidal activity at the rate of 150 g ai/ha by postemergence application. Most promisingly, compound III-l, 3-hydroxy-2-(2-methoxy-7-(methylthio)quinoline-3-carbonyl)cyclohex-2-enone (Ki = 0.009 μM, AtHPPD), had broader spectrum of weed control than mesotrione. Furthermore, compound III-l was much safer to maize at the rate of 150 g ai/ha than mesotrione, demonstrating its great potential as herbicide for weed control in maize fields. Therefore, triketone-quinoline hybrids may serve as new lead structures for novel herbicide discovery.

Synthesis, bioactivity and mode of action of 5A5B6C tricyclic spirolactones as novel antiviral lead compounds

“…The molecules were constructed by the default settings of SYBYL 6.91 software (Tripos Inc.) and optimized with the steepest‐descent algorithm to a convergence criterion of 0.005 kcal mol −1 . The CoMFA steric and electrostatic field energies were calculated by the SYBYL default parameters; an sp 3 carbon probe atom with a charge of +1, 2.0 Å rid points spacing, an energy cutoff of 30.0 kcal mol −1 and a minimum σ (column filtering) of 2.0 kcal/mol …”

Synthesis and herbicidal activity of novel pyrazole aromatic ketone analogs as HPPD inhibitor

“…Among them, triketone HPPD herbicides with triketone and aromatic moieties are the most widely studied . For example, many studies have reported that the modification of the aromatic part of triketone derivatives is an effective way to obtain new inhibitors with improved potency. All the modified triketone derivatives mainly focused on aromatic component, which is replaced by heterocycles, aliphatic side chains, fused heterocycles and fused aromatics …”

Novel HPPD inhibitors: triketone 2H‐benzo[b][1,4]oxazin‐3(4H)‐one analogs

“…) . Among them, mesotrione (Scheme ) is a highly successful representative triketone HPPD herbicide . Established structure–activity relationships indicate that the 2‐benzoylethen‐1‐ol substructure is required for potent HPPD inhibition (Fig.…”

“…Modification of the benzene ring of existing triketone HPPD herbicides has been an effective method of obtaining new HPPD inhibitors. Modified benzene rings of these novel HPPD herbicides include: benzo[ d ]oxazol‐2(3 H )‐one, 2,3‐dihydrobenzo[ b ]thiophene‐1,1‐dioxide, 4 H ‐thiochromene, quinoline, aryloxymethylene and quinazoline‐2,4(1 H ,3 H )‐dione …”

“…[9][10][11] Modification of the benzene ring of existing triketone HPPD herbicides has been an effective method of obtaining new HPPD inhibitors. Modified benzene rings of these novel HPPD herbicides include: benzo[d]oxazol-2(3H)-one, 12 2,3-dihydrobenzo[b]thiophene-1,1-dioxide, 13 4H-thiochromene, 14 quinoline, 8 aryloxymethylene 15 and quinazoline-2,4(1H,3H)dione. 16,17 In our previous work, a series of 2H-1,4-benzoxazin-3-(4H)-one herbicides were designed and synthesized as PPO herbicides.…”