Synthesis and Herbicidal Activity of Novel 1-(Diethoxy-phosphoryl)-3-(4-one-1H-1,2,3-triazol-1-yl)-propan-2-yl Carboxylic Esters

Abstract

A series of novel compounds, namely 1-(diethoxyphosphoryl)-3-(4-ones-1H-1,2,3-triazol-1-yl)propan-2-yl carboxylic esters, were designed on the basis of the diazafulvene intermediate of imidazole glycerol phosphate dehydratase (IGPD) and high-activity inhibitors of IGPD, and synthesized as inhibitors targeting IGPD in plants. Their structures were confirmed by 1 H-NMR, 13 C-NMR, 31 P-NMR and HR-MS. The herbicidal evaluation performed by a Petri dish culture method showed that most compounds possessed moderate to good herbicidal activities. Six compounds were chosen for further herbicidal evaluation on barnyard grass by pot experiments. 1-(Diethoxyphosphoryl)-3-(4-phenyl-1H-1,2,3-triazol-1-yl)propan-2-yl 2-(naphthalen-1-yl)acetate (5-A3) and ethyl 1-(2-acetoxy-3-(diethoxyphosphoryl)propyl)-1H-1,2,3-triazole-4-carboxylate (5-B4) showed good herbicidal activities. Compared with the compounds with the best herbicidal activity ever reported, both compounds 5-A3 and 5-B4, which can inhibit the growth of barnyard grass at the concentration of 250g/hm 2 , efficiently gave rise to a nearly 4-fold increase of the herbicidal potency. However, their herbicidal activities were lower than that of acetochlor (62.5 g/hm 2 ) in the pot experiments.

New 1,2,3‐triazole‐based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations

“…Thus, 1,2,3‐triazole rings are broadly applicable and can be used in compounds such as antiparasitic, anticarcinogenic, antiviral, bactericidal, antiepileptic, enzyme inhibiting and sleep regulating compounds. The literature also describes other applications for these compounds, for example, in explosives and agrochemicals . The 1,2,3‐triazole 1,4‐disubstituted rings are easy to obtain using “click chemistry” and, as click chemistry was conceived, it has had a great impact in many areas of modern chemistry .…”

Crystal Structures Reveal that the Reaction Mechanism of Imidazoleglycerol-Phosphate Dehydratase Is Controlled by Switching Mn(II) Coordination

“…These structures, and other biochemical data, have revealed that, unlike other enzymes, where Mn 2+ can be exchanged with Mg 2+ or Zn 2+ with little effect on activity ( Andreini et al., 2008 ), IGPD has both a structural and mechanistic requirement for manganese ( Petersen et al., 1997 ). Analysis of the IGPD1 structure, coupled with the observation that triazole-phosphonate compounds are potent inhibitors of the enzyme ( Hawkes et al., 1993; Jin et al., 2015; Lindell et al., 1996; Mori et al., 1995 ), has suggested that the reaction ( Figure 1 A) proceeds via an initial high-energy deprotonation of the substrate imidazole ring (p K a ∼14.5) to yield an anionic imidazolate ( Walba and Isensee, 1961 ), which is then converted to the product via diazafulvene and enol intermediates. Since the substrate lacks a carbonyl or imine adjacent to the leaving proton, which is thus non-acidic, IGPD uses an unusual mechanism for catalysis that is distinct from other dehydration reactions that have been reported to date ( Glynn et al., 2005 ).…”

Targeting Metalloenzymes for Therapeutic Intervention

“…1117,1128 Nevertheless, modification of this moiety allows for further synthetic exploration of new active site pockets and provides a handle for the modification of physiochemical properties for this class of inhibitor. 1128 It remains unclear if compounds containing an amine or amide group are able to coordinate to the Mn 2+ ion in the same manner as diazafulvene, as structural characterization of theses inhibitors has not been reported. However, it is likely that hydroxyl, amine, amide, and ester groups at this position are able to engage in hydrogen bonding interactions with the proximal A’ Glu21 residue.…”