Azoxystrobin
Prochloraz
-
-
-
-
100
-
95
P. cubensis: Pseudoperonospora cubensis; E. graminis: Erysiphe graminis; C. gloeosporioides: Colletotrichum gloeosporioides; P. sorghi:
Puccinia sorghi. -: not detected.
The in vivo fungicidal activity was evaluated according to the procedures (Section 1.2 in Supporting information) [27-29] and
presented in Table 1. These data indicated that the chiral acids (Z, R)-2 and (Z, S)-2 and their esters have much higher activities with
the inhibitory rates of 80%-100% than the chiral acid (E, R)-2 and itsester 4, the ester (E, S)-4 with the control rates of 0-60% against P.
cubensis except (E, S)-2 with 100% inhibitory rate; the chiral acids (Z, R)-2 and (Z, S)-2 have much higher activities with the
inhibitory rates of 60%-100% than the chiral acid (E, R)-2, (E, S)-2 and all four ester 4 with the inhibitory rates of 0-50% against E.
graminis, P. sorghi and C. gloeosporioides. These data also showed that the chiral acids have better activities than their esters. The
activities of the chiral acids with Z-configuration of double bond are better than those with E-configuration, and the activities of the
chiral acids with S-configuration of chiral alcohol are better than those with R-configuration. Except against P. sorghi, the chiral acids
(Z, S)-2 showed the same or even better activities against P. cubensis, E. graminis and C. gloeosporioides as that of the positive control.
Based on the above data, the chiral acid (Z, S)-2 is a good lead compound with a broad spectrum of fungicidal activities, the
configurations of the olefin’s double bond and the chiral alcohol play a crucial rule for the fungicidal activities.
In conclusion, the four isomers of 6,7-dihydroxy-3,7-dimethyloct-2-enoic acid and their esters were synthesized via Sharpless
asymmetry dihydroxylation as the key step in 35.0%-48.0% overall yields with 91.9%-97.7% ee values for esters 4 and 31.3%-36.4%
overall yields with 90.3-97.5% ee values for acids 2, respectively, using cis- and trans-geraniol as the raw materials. Their structures
1
13
were characterized by H NMR, C NMR and HR-ESI-MS data. The in vivo bioassay results showed that the chiral acids (Z, S)-2 is a
good lead compound with 80%-100% inhibitory rates against P. cubensis, E. graminis, P. sorghi and C. gloeosporioides at 400 µg/mL.
Acknowledgments
We thank the National Natural Science Foundation of China (Nos. 21772229, 21172254) for the financial support. The bioassay
section of the Sinochem Agrochemicals R&D Co., Ltd. at Shenyang performed the bioassay evaluation, and they were appreciated for
their kind help and discussion.
References
[
[
[
[
[
[
[
[
[
1] L. Gabriela, N.I.P. Gallardo, G.M. Cabrera, Phytochem. Lett. 1 (2008) 155-158.
2] Y. Yang, J.Z. Jiang, L.B. Qimei, et al., Molecules 15 (2010) 7075-7082.
3] A. F. Burton, D. McLean, US 5175190, 1992-12-29.
4] J. Chen, C.L. Zhu, H.Y. Xu, X. Ni, P.M. Yang, Chin. J. Pharm. 41 (201 0) 504-508.
5] K.Y. Lee, S.H. Kim, S.H. Sung, Planta Med. 74 (2008) 867-869.
6] H.B. Dong, M.Y. Yang, J.Z. Jiang, M.A. Wang, J. Asian Nat. Prod. Res. 15 (2013) 880-884.
7] J. Zhao, H.B. Dong, M.Y. Yang, et al., J. Asian Nat. Prod. Res. 16 (2014) 312-317.
8] H.B. Dong, M.Y. Yang, B. Tang, M.A. Wang, Chin. J. Org. Chem. 34 (2014) 2350-2353.
9] M.A. Wang, H.B. Dong, M.Y. Yang, Chinese Patent, CN 103012357A, 2012-12-28.
[
[
10] H.C. Kolb, M.S. Van Nieuwenhze, K.B. Sharpless, Chem. Rev. 94 (1994) 2483-2547.
11] H.B. Dong, M.Y. Yang, X.T. Zhang, M.A. Wang, Tetrahedron: Asymmetry 25 (2014) 610-616.
[
[
12] M.M. Heravi, V. Zadsirjan, M. Esfandyari, T.B. Lashaki, Tetrahedron: Asymmetry 28 (2017) 987-1043.
13] X.Y. Jiang, X.H. Xu, F.L. Qing, Chin. Chem. Lett. 25 (2014) 1115-1120.
14] Q.F. Wang, F. Chen, Y. Zhao, X.Y. Li, S.Y. Zhang, Chin. Chem. Lett. 20 (2009) 763-766.
15] D.G. Liu, J.J. Xue, Z.X. Xie, et al., Chin. Chem. Lett. 20 (2009) 775-778.
16] X.M. Zhang, A. Archelas, R. Furstoss, J. Org. Chem. 56 (1991) 3814-3817.
17] A.D. Fourneron, A. Archelas, R. Furstoss, J. Org. Chem. 54 (1989) 4686-4689.
18] F. Felpin, C. Lory, H. Sow, S. Acherar, Tetrahedron. 63 (2007) 3010-3016.
19] G. Vidari, A. Dapiaggi, G. Zanoni, L. Garlaschelli, Tetrahedron Lett. 34 (1993) 6485-6488.
20] J. Mori, M. Iwashima, M. Takeuchi, H. Saito, Chem. Pharm. Bull. 54 (2006) 391-196.
21] G. Edegger, S. F. Mayer, A. Steinreiber, K. Faber, Tetrahedron. 60 (2004) 583-588.
22] R.B. Boar, K. Damps, J. Chem. Soc. Perkin Trans. I. 8 (1977) 709-712.
[
[
[
[
[
[
[
[
[
[
[
[
23] T.J. Donohoe, P.R. Moore, M.J. Waring, Tetrahedron Lett. 38 (1997) 5027-5030.
24] D. Xu, C.Y. Park, K.B. Sharpless, Tetrahedron Lett. 35 (1994) 2495-2498.
[
[
[
[
27] A.Y. Guan, C.L. Liu, W. Chen, et al., J. Agric. Food Chem. 65 (2017) 1272-1280.
28] A.Y. Guan, M.A. Wang, W. Chen, et al., J. Fluorine Chem. 201 (2017) 49-54.
29] A.Y. Guan, M.A. Wang, J.L. Yang, et al., J. Agric. Food Chem. 65 (2017) 10829-10835.