Synthesis metalaxyl

The biochemical mode of action has been studied by several authors (16, 18). It appears that metalaxyl inhibits RNA synthesis by Interference with template-bound and a -amanitin-insensitive RNA polymerase action (15). 

Metalaxyl or methyl-N-(methoxyacyl)-N-(2,6-xylyl)-DL-alaninate Acylalanine Inhibits protein synthesis in fungi, systemic with protective action Control of air- and soil-bome diseases on crops 11-29... 

There have been many other independent reports of excellent S/C ratios using rhodium DuPHOS systems. For the synthesis of an (R)-metalaxyl intermediate 19 [21], a turnover number of 50000 has been demonstrated using Me-DuPHOS-Rh. Hoffmann la Roche have reported the Et-DuPHOS-Rh-catalyzed hydrogenation at S/C 10000-20000 of a cyclic enol acetate 21 to provide an intermediate 22 to Zeaxanthin in 98% ee [22] (Fig. 12). 

In phenylamide-resistant strains, phenylamides are not able to inhibit ribosomal RNA synthesis, as is indicated by the inability of metalaxyl to interfere with uridine incorporation in a phenylamide-resistant strain of P. megasperma f. sp. megasperma obtained in the laboratory after mutagenic treatment (14) and a phenylamide-resistant strain of Phytophthora infestans (Table III) originating from a potato field (15). 

This indicates that the apparent dissociation constants for benalaxyl and metalaxyl are similar. The binding site has a lower affinity for cyprofuram and oxadixyl, which is in agreement with the lower activity of these compounds against RNA synthesis measured as [ H]uridine incorporation by mycelium (121. 

The fungicides inhibited protein and nucleic acid synthesis. RNA production was particularly affected. There was some evidence of a reduction in nuclear division. The primary effect of metalaxyl and furalaxyl probably involves impaired biosynthesis of RNA so that mitosis is inhibited (Kerkenaar, 1981 Fischer and Hayes, 1982). 

Newest Aspects of Nucleic Acid Synthesis Inhibitors - Metalaxyl-M... 

Scheme 23.1. Synthesis of metalaxyl-M 1 starting from (S)-lactic acid methyl ester (chiral pool).

The phenylamide fungicides, including metalaxyl and metalaxyl-M, inhibit ribo-somal RNA synthesis, specifically RNA polymerization (polymerases). In myce-... 

The phenylamide fungicides affect especially hyphal growth and the formation of haustoria and spores in oomycetes [22]. Since spores contain many ribosomes to support early growth stages, RNA synthesis is fully operational only after spore germination therefore, later development stages are most sensitive [19]. As a consequence of RNA inhibition, the precursors of RNA synthesis (i.e., nucleoside triphosphates) are accumulated. They activate j8-l,3-glucan synthetases, which are involved in cell wall formation [19] with the result that metalaxyl-treated hyphae often produce thicker cell walls than untreated ones. 

Metalaxyl is a member of a class of compounds that structurally resemble the chloroacetani-lides however, it is a systemic fungicide. Diflubenzuron is representative of a class of insecticides that owe their action to inhibition of chitin synthesis by the developing insect. Metalaxel and diflubenzuron are good examples of compounds prepared by the synthesis chemist as herbicide candidates that have commercial levels of activity in entirely different applications. Such examples point out the need for a balanced synthesis and screening program for the development of new agrochemicals. 

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