Penthiopyrad

Penthiopyrad [218,219] is a new carboxamide fungicide under development by Mitsui Chemicals that shows good activity against Botrytis, powdery mildew, and apple scab. 

The key intermediate for the synthesis of penthiopyrad, l-methyl-3-trifluoro-methylpyrazole-4-carboxylate 29, is prepared as shown in Scheme 11.8 by treatment of ethyl trifluoroacetate with ethyl cyanoacetate in the presence of a base such as sodium methoxide to give butenoate 27 followed by treatment of methyUiydrazine sulfate in the presence of trifluoroacetic acid. The deamination of 28 by diazotization-deazotization gives the key intermediate 29. The final steps to penthiopyrad involve amination of ester 29 with the appropriate 2-alkenyl-3-aminothiophene derivative followed by hydrogenation using a noble metal catalyst. ... 

Furthermore, penthiopyrad has a mode of action different from that of many commercial fungicides used on these kinds of diseases. No cross resistance has... 

Figure 2. Inhibitory activity of penthiopyrad on sporulation of Botrytis cinerea.

Penthiopyrad interrupts electron transport in the mitochondrial respiratory chain. As a result of this effect, the fungus cannot produce vital energy in the form of ATP. 

Table 3. Mitochondrial Complex II inhibition activity of penthiopyrad as indicated by I50 (nM).

Penthiopyrad showed high inhibitory activity against the enzyme Complex II derived from not only Rhizoctonia solani but also Botrytis cirterea and Fusarium oxysporum. 

From these trials, it became clear that penthiopyrad shows no cross-resistance to DM I fungicides or strobilurin fungicides. 

Carboxin is the one of the oldest members of the carboxanilide fungicide family and has been used as an important seed treatment fungicide for about 40 years. A new and more active fungicide, penthiopyrad, with the same mode of action as carboxin, has been discovered where its antifungal spectrum is much broader. 

Although the carboxanilide family is one of the oldest groups of fungicides, the discovery of penthiopyrad will open a new avenue for the future research and development of novel compounds from this family of fungicides. The biological properties and favorable attributes of penthiopyrad as a commercal candidate are as follows ... 

We thank Dr. Miyoshi of the Department of Applied life Science, Kyoto University, for the study of the mode of action of penthiopyrad, and Dr. Ishii of National Institute of Agro-Environmental Sciences for work on the resistant fungi. 

For penthiopyrad (10) a laboratory-scale synthesis has been published in which the branched alkyl residue on the thiophene ring was generated from an acetyl group by addition of methylmagnesiumbromide and subsequent reduction by triethylsilane [18]. 

Fluoro- and flnoroalkylpyrazole templates are also present in important agrochemicals, two examples being the marketed fungicide penthiopyrad [96] (Fig. 7a) and the insecticidal anthranilic diamide (Fig. 7b) [97]. Fnstero and co-workers prepared a small set of analogues of the commercially available acaricide tebufen-pyrad with several fluorinated side chains at the pyrazole C-3 [98]. Some of these compounds displayed higher acaricidal activity than the parent compound tebufen-pyrad (Fig. 7c). 

Culbreath AK, Brenneman TB, Kemerait RC Jr, Hammes GG (2009) Effect of the new pyrazole carboxamide fungicide penthiopyrad on late leaf spot and steam rot of peanut. Pest Manag Sci 65 66-73... 

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