Herbicides optical activity

An even more impressive example of catalytic efficiency has recently been disclosed by Novartis (Bader and Bla.ser, 1997). The key step in a proce.ss for the synthesis of the optically active herbicide, (S)-metolachlor involves asymmetric hydrogenation of a prochiral imine catalysed by an iridium-ferrocenyldipho-sphine complex (see Fig. 2.36). 

Quite a wide range of substrates 100 could be converted into products 101 with high ee values since it is known that the N-protecting group of 101 can easily be cleaved, the approach represents a formal synthesis of optically active amines. It remains to be seen if this iridium/sulfoximine combination also opens up an alternative access to industrially relevant products such as the herbicide (S)-metolachlor produced by Syngenta [80]. 

More than half of all drugs on the market are asymmetric molecules. Many of these are administered as racemates. Since biological recognition systems are based on optically active molecules, the two enantiomers of a racemic drug may interact by different mechanisms with these systems. One of the enantiomers may exert pharmacologically different or unwanted side effects [1-3]. The same is true for racemic pesticides and herbicides often only one of the enantiomers possesses the desired activity. 

The hydrogenation of olefins with soluble metal complexes has been studied extensively" 5. This intensive study seems anomalous because soluble catalysts are seldom used for olefin hydrogenation in industry and in organic synthesis. The importance of homogeneous catalysts is great in asymmetiic reactions (L-Dopa, Dual herbicide synthesis) where the high stereoselectivity of optically active catalysts is the major advantage. 

Mackay SP, O Malley PJ. Molecular modelling of the interaction between optically active triazine herbicides and photosystem II. Z Naturforsch 1993 48c 474-481. 

Quizalofop-ethyl(Ci9Hi704N2Cl hereafter abbreviated as QE) a useful material for the production of herbicides it is an optically active compound and has two known... 

The inclusion complexes formed between p-cyclodextrin (p-CD) and various optically active solutes (drugs and herbicides, Table 8.14) were modeled and refined using molecular modeling methods. The interaction energies of the complexes formed were calculated for both enantiomers and were correlated with the experimental retention data measured by normal-phase HPLC. A model cyclodextrin containing 441 atoms, 469 bonds, and 3513 connectors... 

The Novartis process for the synthesis of the optically active herbicide(s)-metachlor (Blaser and Spindler, 1998) involves a chiral metal complex as a catalyst (see Fig. 3.11). An iridium(l) complex of a chiral ferrocenyldiphosphine catalyzes the asymmetric hydrogenation of a prochiral imine, a key step in the process. The sub-strate/catalyst ratio for this step is 750,000, tvith high turnover, thus making the process industrially viable. 

FIGURE 3.11. Novartis process for the synthesis of the optically active herbicide. 

All substituted alkylphosphonates lA-IJ and IVC-IVE studied or reported previously were only based on their racemic forms. Considering the importance of chirality for herbicidal active, the synthesis and the biological activities of their optical counterparts would be very important. The methods of asymmetric synthesis of both chiral 1-hydroxyphosphonates and cyclic 1-hydroxy phosphonates, and several optically active 1 -(substituted phenoxyacetoxy)alkylphosphonates were hence set up. So far, several series of optically active 1-(substituted phenoxyacetoxy) alkylphosphonates including lA, IC, IE, IF series were prepared (Scheme 1.34) and their biological activities were evaluated. Their asymmetric synthesis, enantiomeric selectivity in herbicidal activity, acute aquatic toxicity, and SAR discussion are summarized in Chap. 6. 

Up to now, our study on all these chiral 1-substituted alkylphosphonates only limited to their racemic forms. Considering the importance of chirality for herbi-cidal active, it would be very interesting to examine the contribution of the optical counterparts to their biological activity. As our work aimed at the herbicidal effect of the optically active isomer of chiral 1-substituted alkylphosphonates, we first attempted to set up an efficient method to prepare the isomers of 1-substituted alkylphosphonates with optical activity. 

At this stage, we made an effort to prepare two enantiomers of open-chain 1-(substituted phenoxyacetoxy)- -(substituted phenyl)methylphosphonates lA, IE and IF series. The herbicidal activity of these optically active substituted benzyl phosphonates lA, IE, and IF were examined. In this section, the synthesis and herbicidal activity of optically active substituted benzylphosphonates lA, IE and IF are introduced. The structure-activity relationships of these optically active compounds together with their racemates are discussed. 

As stated in Chap. 2, some chiral 1-(substituted phenoxyacetoxy)alkylphosphonates lA, IE, and IF exhibited significant post-emergence herbicidal activity against dicotyledons, but the examination of herbicidal activity was only limited their racemic forms. It would be very interesting to examine the contribution of optical active isomers in their herbicidal activity. 

In order to explore the possible difference between two enantiomers in herbicidal activity, a set of experiments was performed to evaluate optically active 1-(substituted phenoxyacetoxy)alkylphosphonates lA, IE, and IF. The herbicidal bioassay was carried out according to the method mentioned in Chap. 9. The influences of molecular chirality on herbicidal activity are discussed as follows. 

Herbicidal Activity of Optically Active 1-(Substituted Pbenoxyacetoxy)alkylphospbonates lA... 

A) Pre-emergence herbicidal activity of optically active compounds lA... 

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