Protox

Protoporphyrinogen oxidase (protox), crop resistance to, 73 361-362 Prototype pilot plants, 79 459 Protoveratrine A, 2 105 Prourokinase, 5 175, 178... 

Diphenyl ether herbicides. The diphenyl ether class of herbicides belongs to a broader area of herbicides known as protoporphyrinogen oxidase (Protox) herbicides [20,21], Diphenyl ether herbicides were initially introduced over four decades ago in the 1960s with the discovery of nitrofen by Rohm and Haas (now Dow AgroSciences) [22] and bifenox by Mobil [23], These early diphenyl ether herbicides did not attain a significant role in the control of weeds in commercial crops until the 1970s, with the introduction of the trifluoromethyl compounds oxyfluorfen [24] and acifluorfen-sodium [25], Replacement of the chlorine with a trifluoromethyl group resulted in a dramatic increase in the herbicidal properties of these compounds, in terms of both potency and the spectrum of weeds controlled. 

Pyraflufen-ethyl (Ecopart ) [114] is a broadleaf weed postemergence herbicide for use in cotton and cereals. Pyraflufen belongs to the family of herbicides that inhibit the Protox enzyme. 

Fig. 31. Structure-activity of A/-substituted triazolinone Protox herbicides.

Protox herbicides. A number of Protox herbicides share a 2-fluorophenyl group. Initial investigations into an alternative synthesis of 2-fluoro-4-chlorophenyl triazolinones resulted in the very promising use of newer fluorinating reagents. The actual synthesis of carfentrazone-ethyl involved the use of 2-fluoroaniline as the starting material (Fig. 35) [150],... 

A number of recent herbicide entries include bencarbazone [185], pyrasulfotole [186], and pyrimisulfan [187], Bencarbazone, whose ISO common name was approved in 2005, has all the features associated with Protox herbicides, particularly that of the Protox herbicide sulfentrazone. Pyrasulfotole is a newly developed herbicide from Bayer CropScience for use on cereals. Pyrimisulfan, a difluoromethylsulfonamide-containing, herbicide, is a new ALS herbicide for the control of perennial weeds. 

G. Theodoridis, J.T. Bahr, F.W. Hotzman, S. Sehgel, D.P. Suarez, New generation of protox-inhibiting herbicides, Crop Prot. 19 (2000) 533-535. 

Many photobleaching herbicides act by inhibiting the enzyme protoporphyrinogen oxidase (Protox), which catalyzes the last step in common between chlorophyll and heme biosynthesis. Usnic acid shares some structural features in common with these herbicides, such as the diphenyl ether scaffolding. The inhibitory activity of (-)-usnic acid on Protox was similar to that of the herbicide, acifluorfen, (I50 ca. 3 pM). However, these compounds did not displace acifluorfen from its binding site on Protox (data not shown), indicating that this natural product interacts with Protox differently than other photobleaching inhibitors. 

Lichens containing usnic acid may exhibit phytotoxic activity. In nature, (-)-usnic acid may decrease interspecific competition by inhibiting growth of seedlings in the canopy. Since it is primarily an HPPD inhibitor and secondarily inhibits Protox, there may be a decreased chance for resistance in those competing species. 

Figure 9.3. The two faces of pyrrolizidine alkaloids (PAs). The non-toxic PA JV-oxide is easily converted into the protoxic free base in the gut of herbivores or predators.

Triazole-sulfonamide herbicides are egosterol biosynthesis inhibitors, and include prop-iconazole (100) and flusilazole (101). Apart from a range of sulfonamides introduced in 1992, no further important developments occurred until the introduction of protox-inhibiting herbicides, mainly diphenyl ethers and cyclic imides, the latter including aryl... 

Protox. [Protameen] Ethoxylated alkyl amines cosmetics ingredients. 

Figure 2. A Agrophore model derived from 318 Protox inhibitors.

Figure 3. Statistics derived from a comparative molecular similarity indices analysis (CoMSIA) [26] for the agrophore model shown in Figure 2A. The graph depicts the predictive power of a leave-one-out cross-validation procedure for 318 Protox inhibitors (SDEP = standard errorof prediction).

Figure 4. Sterically favorable volume derived from a 3-D QSAR study for Protox inhibitors. Molecules totally enclosed by the volume are, with respect to this particular property, more active (left) than derivatives with protruding residues (right).

Figure 6. Binding site region of Protoporphyrinogen IX Oxidase 2 [Protox, pdb code ISEZ) with the co-crystallized inhibitor /NH (ball and sticks representation), the critical amino acid residue arginine (Arg) and the co-factor FAD. Re-docked solutions are indicated inside (int) and outside (ext) of the detected binding pocket.

A reasonable result is shown for the BASF Protox inhibitor BPI (Figure 7). In this solution, the acid function of INH is mimicked by the nitrogen atom of the benzothiazole moiety of BPI forming the crucial hydrogen bond to arginine. This facilitates a good match for the trifluoromethyl-pyrazol of INH and the trifluoromethyl-pyrimidinedione of BPI. 

Figure 7. Docking solution for BASF s inhibitor BPI to the Protox binding site. For clarity, INH and BPI are superimposed indicating the relative orientation and mimicking functions for complexation with the critical arginine residue (Arg).

Emar Felling zinc oxide Flores de zind Flowers of zinc Green seal-8 Hubbuck s white Kadox 15 Kadox 72 Kadox-25 ozide Ozlo Permanent white Philosopher s wool Powder base 900 Protox types 166, 167, 168, 169, 267, 268 Red seal-9 Snow white ... 

The lack of clear selectivity of several commercially significant row crops was overcome following the discovery of several highly active and selective Protox herbicides such as the post-emergence soybean selective herbicide fomesafen 7 (Flex , Flexstar , Reflex ) [1, 2], introduced in 1983 by ICI Plant Protection Division, and the soybean selective pre-emergence herbicides F5231, compound 14 [3-5], and sulfentrazone (15) (Authority , Boral , Capaz ) [6-8] introduced by FMC in 1991. 

In this chapter, we discuss recent developments and challenges in the field of Protox-inhibiting agrochemicals and place those agrochemicals in the context of research done in this area of chemistry in the past four to five decades. 

The diphenyl ether nitrofen (1) [24], introduced in 1963 by Rohm and Haas, now Dow AgroSciences the oxadiazolinone oxadiazon (2) [25, 26] (Explorer , Herbstar , Romax , Ronstar ), introduced in 1968 by Rhone-Poulenc and the tetrahydrophthalimide chlorophthalim 3 [27], introduced in 1972 by Mitsubishi, represent the earliest examples of Protox herbicides (Fig. 3.2). Though all three classes are chemically quite different, they share a common mode of action, inhibition of the protoporphyrinogen oxidase enzyme, though this was not known until the late 1980s. 

Following the discovery of the herbicidal activity of nitrofen (1) in 1963, intense research by several agrochemical companies resulted in a vast number of highly active and diverse chemistries [28, 29]. As mentioned earlier, the diphenyl ether chemistry represents the first class of Protox herbicides. Replacement of the aromatic 4-chloro group with a trifluoromethyl, as is the case with oxyfluorfen (5) (Goal ) [30], resulted in a significant improvement in biological activity, and 2-... 

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