Hydrophobicity and Systemic Activities of Fungicidal Triazoles and

Chapter 8

Hydrophobicity and Systemic Activities of Fungicidal Triazoles and Bleaching Herbicidal Compounds 1

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Downloaded by UNIV LAVAL on July 14, 2016 | http://pubs.acs.org Publication Date: May 5, 1995 | doi: 10.1021/bk-1995-0606.ch008

Shizuya Tanaka, Masahiro Takahashi, Yuji Funaki , Kazuo Izumi , Hirotaka Takano, and Masakazu Miyakado Agricultural Chemicals Research Laboratory, Sumitomo Chemical Company, Ltd., 4-2-1 Takatsukasa, Takarazuka, Hyogo 665, Japan

Two examples are described to show that the systemic translocation as well as the systemic activity is markedly lowered when the log Ρ value of series of analogs exceeds a boundary located between 4 and 5. Triazole fungicides such as uniconazole, diniconazole, and their analogs were active against powdery mildew on barley by foliage application. By soil application, however, the fungicidal activity depended on whether the log Ρ value of the compounds is lower or higher than 4. Herbicidal compounds with bleaching activity such as 3-phenoxybenzamides, fluridone and its analogs, norflurazon, difunon, flurtamone, and diflufenican showed three types of bleaching patterns on expanded cotyledons of radish after seed treatment. In spite of their structural diversity, variations in the bleaching pattern was clearly understandable in relation to the log Ρ value of the compounds. When the log Ρ value of the compounds was between 4 and 5, pronounced changes in the systemic activities occurring through the root-to-shoot as well as the lateral and translaminal translocations were observed. The systemic translocation of agrochemicals in plants is a very important problem. For agrochemicals applied at remote locations from the targeted zone in plants, the systemicity is a prerequisite for their bioactivity. Although the translocation of agrochemicals in plants has been shown to be connected to their hydrophobicity in terms of the log Ρ value (P: 1-octanol / water partition coefficient) in certain respects (7,2,3,4,5), "the systemic activity" of agrochemicals in relation to their systemicity in plants has not always been well understood (3). In this chapter, we selected two topics dealing with fungicidal activity of triazole compounds and bleaching activity of

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Current address: Technology & Research Management Office, Sumitomo Chemical Company, Ltd., 2-27-1 Shinkawa, Chuo-ku, Tokyo 104, Japan Current address: Farmchemicals & Materials Division, Sumitomo Chemical Company, Ltd., 4-5-33 Kitahama, Chuo-ku, Osaka 541, Japan

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0097-6156/95/0606-0107$12.00/0 © 1995 American Chemical Society Hansch and Fujita; Classical and Three-Dimensional QSAR in Agrochemistry ACS Symposium Series; American Chemical Society: Washington, DC, 1995.

108

CLASSICAL AND THREE-DIMENSIONAL QSAR IN AGROCHEMISTRY

herbicidal compounds. In both cases, systemic activity of agrochemicals is controlled greatly by their log Ρ value. There seems to exist a boundary in the log Ρ value above which the systemicity decreases drastically so that the systemic activity almost disappears under certain conditions.


Fungicidal Triazole Compounds

Triazole compounds, uniconazole and diniconazole (Figure 1), are not only fungicidal but also exhibit a plant growth regulatory activity (PGR activity) as their racemic form. During the course of their biological evaluation as agrochemicals, we observed a large difference in systemic activity between these two compounds. Limited systemicity of diniconazole as a candidate of novel fungicide was an important factor to reduce and separate the P G R activity. On the other hand, the higher xylemmobility of uniconazole was essential as the PGR for its use as granular formulations in the paddy field. After extensive toxicological and environmental studies, two optically active compounds, uniconazole Ρ (the S-isomer of uniconazole) as a PGR, and diniconazole M (the /^-isomer of diniconazole) as an agricultural fungicide, were eventually marketed. Both optically active triazoles have been manufactured industrially by enantioselective reduction of their corresponding ketone precursors (6). Resolution into the optical isomers has resulted in a reduction of the application rate and an enhanced selectivity between target and non-target organisms. Moreover, an almost complete separation of fungicidal and PGR activities has been accomplished, i.e., uniconazole Ρ shows no significant fungicidal activity and diniconazole M has almost no PGR effect (7). In the following sections, however, all experimental results were obtained using racemic compounds.

CI

CI

CI

uniconazole

diniconazole

CI

CI

CI

uniconazole Ρ [5'(+)-isomer] use: plant growth regulator inhibition: gibberellin biosynthesis

diniconazole M [/?(-)-isomer] use: fungicide inhibition: ergosterol biosynthesis

Figure 1. Uniconazole, Diniconazole, Uniconazole P, and Diniconazole M .

Hansch and Fujita; Classical and Three-Dimensional QSAR in Agrochemistry ACS Symposium Series; American Chemical Society: Washington, DC, 1995.


8.

TANAKAETAL.

Fungicidal Triazoles & Bleaching Herbicidal Compounds 109

Translocation of Uniconazole in Cucumber: Cucumber treated with radiolabeled uniconazole (log P: 3.77) at the roots is shown in Figure 2. It is suggested that uniconazole is highly xylem-mobile from roots. Within 2h, it moves into veins of the first and second foliage leaves. It spreads over all of the parts of these foliage leaves and cotyledons after 6h, and reaches to the third foliage leaf 24h after the start of the treatment. When a central area on the second foliage leaf was treated by uniconazole, on the other hand, the translocation through xylem across the cuticular membrane is not observed clearly, but it is laterally mobile and maybe translaminally mobile as well to a lower extent as shown in Figure 3. After 2h, the xylem-translocation toward the leaf tip occurs first, but a lateral translocation is observed only after 6, 24, and 48h. The radioactive area expands about 4 fold during the 48h treatment. The lateral translocation on the leaf is much slower than the root-to-shoot translocation. This is probably due to the fact that, once uniconazole is trapped in the cuticular membrane from the leaf surface, it is slow to diffuse out and translocate again. Such hydrophobic agrochemicals as PCNB (log P: 5.0) and fluvalinate (log P: 5.5) are reported to be incorporated into cucumber leaf cuticles isolated with enzymatic treatments and to reach saturation rapidly, but have difficulty getting across the cuticular membrane (8). Translocation through phloem to other leaves and roots of uniconazole was not observed. Systemic Activity of Triazole Compounds: Protective activity of uni(dini)conazole analogs against the powdery mildew on barley are shown in Table I. Uniconazole and compounds 1 and 2 were highly active on foliage as well as soil application. As

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Figure 2. Translocation of C-Uniconazole in Cucumber by the Root Treatment. (A): Oh. (B): 2h. (C): 6h. (D): 24h. (E): 48h.



110


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Figure 3. Translocation of C-Uniconazole in Cucumber by the Foliage Treatment. (A): Oh. (B): 2h. (C): 6h. (D): 24h. (E): 48h. (F): Photograph of cucumber used in this experiment. indicated above, the translocation of uniconazole is very slow after the foliage treatment, but this is when the application has been made topically on leaves. With the spray on the entire foliage, uniconazole was believed to be distributed in plants much faster and the difference between soil and foliage treatments does not seem to be significant. Among the four compounds, diniconazole (log P: 4.30) was not active by soil application. Because of the highest log Ρ value, the soil adsorption of diniconazole is also highest (9). Under conditions in which the soil adsorption is not critical, however, we estimated that its root-to-shoot translocation is still limited. The application of diniconazole on roots of barley seedlings did not show evidence for its significant mobility. The PGR activity by soil application is also shown in Table I. Diniconazole exhibited only a very low PGR activity compared with the other three compounds. Table I shows that the systemic activity through the root-to-shoot translocation of these triazole compounds decreases drastically when their log Ρ value exceeds 4. Systemic Activity and Hydrophobicity: To examine the relationship between the log Ρ value and the systemic activity of uni(dini)conazole analogs further, we prepared a number of derivatives. For those in which the 4-C1 substituent on the benzene ring of uniconazole was replaced by a variety of less hydrophobic substituents, the protective activities against the powdery mildew on barley and the brown rust on wheat were measured by the foliage application (10) as summarized in


8. TANAKA ET AL.

Fungicidal Triazoles & Bleaching Herbicidal Compounds 111

Table I. Fungicidal and PGR Activities of Triazole Compounds

Ν

>

^— N

Powdery Mildew on Barley


unic

c

X

logP

4-C1

3.77

d

4

4

3

4

4

4

4

e

4

50

5

12.5 3.1 (mgA)

5 (g/a)

1.25 0.3 (mg/pot)

1

2-F,4-Cl

3.91

4

4

4

4

4

3

2

4-Br

3.92

e

4

3

2

4

3

2

3

4.30

d

4

4

4

1

0

0

0

dinic

f

2,4-Cl

2

b

soil

soil

foliage Compd

PGR

3

a

Disease control, 0: the lower is the systemicity. More important is the fact that there is a boundary in the log Ρ value between compound 2 (log P: 3.92) and diniconazole (log P: 4.30) above which an abrupt decrease in the systemic activity is observed.


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Table II. Fungicidal Activities of Uniconazole and Its Analogs

3

X

Wheat brown rust


Barley Compd

X

3

SOCH

log/*

50

12.5 (mgA)

3.1

50

1.47

4

3

1

0

1.83

0

0

0

3

c

12.5 3.1 (mg/1) 0

0

0 _d

0

-

-

0

-

-

-

4

NH

5

NHCOCH3

2.08

0

0

0

6

OH

2.39

0

0

0

7

CN

2.49

4

3

1

3

2

1

N0

2.80

4

2

1

0

0

0

2.98

2

0

0

0

-

4

8

2

2

OCH3

9

COOC2H5

10 unic

e

3.56

CI

a

3.77

f

0

0

0

0

-

4

4

3

4

4

b

Adapted from ref. 10. Calculated additively with the CLOGP program on the basis of the value of uniconazole. Disease control, 0:

Hydrophobicity and Systemic Activities of Fungicidal Triazoles and

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