Structure phytoene desaturase inhibitors

Phytoene Desaturase Inhibitors j 197 Table 4.1.2 Structural evolution of phenoxypyridine ethers since 1994. 

Table 35.13 Chemically different classes of phytoene desaturase inhibitors (80-86) (see Fig. 35.20 for the basic structure).

Inhibitors of carotenoid synthesis also lead to chlorophyll destruction by destabilizing the photosynthetic apparatus. Total carotenoid content decreased with increased (-)-usnic concentration (Fig. 1.4). Carotenoid biosynthesis can be interrupted by inhibiting the enzyme phytoene desaturase that converts phytoene to carotenes or by inhibiting the enzyme HPPD responsible for plastoquinone (required for phytoene desaturase activity) synthesis.14 Usnic acid possesses some of the structural features of the triketone HPPD inhibitors, such as sulcotrione (Fig. 1.1C).8 (-)-Usnic acid had a strong inhibitory activity on HPPD, with an apparent IC50 of 70 nM, surpassing the activity obtained with the commercial herbicide sulcotrione (Fig. 1.5). 

If our hypothesis is correct, this hypothetical binding site should also accommodate fluridone, norflurazon and difunone and some possible binding orientations of these molecules are compared with furanone 13 in Figures 7-9. Note that we have attempted to depict the molecules in such a way that key structural features, e.g., the CF3 phenyl and vinylogous amide subunits, occupy the same positions as nearly as possible. Finally, it should be emphasized that considerable further work is required to demonstrate that the furanones actually inhibit phytoene desaturase and to further probe the possibility of a common binding site for the proven inhibitors including those such as fluorochloridone (10) and the m-phenoxybenzamides (4), which do not incorporate the vinylogous amide substructure. 

As a methodology to search for a new lead, we focused on the chemical approach using A,S-heterocycles. This approach led to the evolution of 5-methylene-thiazolidines as the lead to bleaching herbicides. Further structural modifications based on the parent compound resulted in the creation of a new family of bleaching herbicides, 2-(W-difluoroacelylimino)-S-methyl-3-(3-trifiuoromethylphenyl)-l,3-thiazoline, (S-3085) widi potent preemergence herbicidal activity and selectivity on cotton crops. On die basis of biochemical studies, 3-phenylthiazolines have been characterized as a new inhibitor of phytoene desaturase. Facile syndieses of 1,3-thiazolines and the manufacturing process toward S-3085 will be reported in future publications. 

---