Design, Synthesis and Antifungal Activities of Novel Strobilurin Derivatives Containing Pyrimidine Moieties

Strobilurins are one of the most important classes of agricultural fungicides. To discover new strobilurin derivatives with high activity against resistant pathogens, a series of novel -methoxyacrylate analogues were designed and synthesized by integrating substituted pyrimidine with a strobilurin pharmacophore. The compounds were confirmed and characterized by infrared, nuclear magnetic resonance, elemental analysis and mass spectroscopy. The bioassays indicated that most of the compounds (1a-1h) exhibited potent antifungal activities against Colletotrichum orbiculare, Botrytis cinerea Pers and Phytophthora capsici Leonian at the concentration of 50 . Exhilaratingly, compound 1d (R=3-trifluoromethylphenyl) showed better antifungal activity against all the tested fungi than the commercial strobilurin fungicide azoxystrobin.

[1]  K. Ikeda,et al.  Cytological evaluation of the effect of azoxystrobin and alternative oxidase inhibitors in Botrytis cinerea. , 2012, FEMS microbiology letters.

[2]  B. Campbell,et al.  Antifungal activity of redox-active benzaldehydes that target cellular antioxidation , 2011, Annals of Clinical Microbiology and Antimicrobials.

[3]  Rui Liu,et al.  Synthesis, Crystal Structure and Fungicidal Activities of New Type Oxazolidinone-Based Strobilurin Analogues , 2010 .

[4]  Guang Huang,et al.  Design, synthesis and acaricidal activity of novel strobilurin derivatives containing pyrimidine moieties. , 2010, Pest management science.

[5]  Hong Zhang,et al.  Synthesis and biological activity of new (E)-alpha-(Methoxyimino)benzeneacetate derivatives containing a substituted pyrazole ring. , 2010, Journal of agricultural and food chemistry.

[6]  C. Zhan,et al.  Subnanomolar inhibitor of cytochrome bc1 complex designed by optimizing interaction with conformationally flexible residues. , 2010, Journal of the American Chemical Society.

[7]  Zhengming Li,et al.  Design, synthesis and biological activities of new strobilurin derivatives containing substituted pyrazoles. , 2010, Pest management science.

[8]  Changling Liu,et al.  Design, synthesis and fungicidal activity of novel strobilurin analogues containing substituted N-phenylpyrimidin-2-amines. , 2009, Natural product communications.

[9]  Changling Liu,et al.  Design, Synthesis and Fungicidal Activity of Novel Strobilurin Analogues Containing Substituted N-phenylpyrimidin-2-amines , 2009 .

[10]  Wei Huang,et al.  Synthesis, fungicidal, and insecticidal activities of beta-Methoxyacrylate-containing N-acetyl pyrazoline derivatives. , 2008, Journal of agricultural and food chemistry.

[11]  A. Mai,et al.  Synthesis and biological properties of novel 2-aminopyrimidin-4(3H)-ones highly potent against HIV-1 mutant strains. , 2007, Journal of medicinal chemistry.

[12]  Wei Huang,et al.  Synthesis and fungicidal evaluation of novel chalcone-based strobilurin analogues. , 2007, Journal of agricultural and food chemistry.

[13]  S. Abrams,et al.  Design and synthesis of beta-methoxyacrylate analogues via click chemistry and biological evaluations. , 2007, Bioorganic & medicinal chemistry letters.

[14]  Wei Huang,et al.  Design, synthesis, and fungicidal activities of new strobilurin derivatives. , 2007, Journal of agricultural and food chemistry.

[15]  Yan Li,et al.  Stereoselective synthesis and antifungal activities of (E)-alpha-(methoxyimino)benzeneacetate derivatives containing 1,3,5-substituted pyrazole ring. , 2006, Journal of agricultural and food chemistry.

[16]  Yan Li,et al.  Stereoselective synthesis and fungicidal activities of (E)-alpha-(methoxyimino)-benzeneacetate derivatives containing 1,3,4-oxadiazole ring. , 2006, Bioorganic & medicinal chemistry letters.

[17]  Nicholas Fisher,et al.  Re-examination of inhibitor resistance conferred by Qo-site mutations in cytochrome b using yeast as a model system. , 2005, Pest management science.

[18]  T. Okawara,et al.  Inhibitory activities against topoisomerase I and II by isoaurostatin derivatives and their structure-activity relationships. , 2005, Bioorganic & medicinal chemistry letters.

[19]  T. Lundbäck,et al.  Substituted benzylamino-6-(trifluoromethyl)pyrimidin-4(1H)-ones: a novel class of selective human A-FABP inhibitors. , 2004, Bioorganic & medicinal chemistry letters.

[20]  T. Nagata,et al.  Synthesis and structure-activity study of fungicidal anilinopyrimidines leading to mepanipyrim (KIF-3535) as an anti-Botrytis agent. , 2004, Pest management science.

[21]  H. Sierotzki,et al.  Mechanisms influencing the evolution of resistance to Qo inhibitor fungicides. , 2002, Pest management science.

[22]  Mick Hamer,et al.  The strobilurin fungicides. , 2002, Pest management science.

[23]  T. Anke,et al.  Strobilurins: Evolution of a New Class of Active Substances. , 1999, Angewandte Chemie.

[24]  P. Worthington,et al.  β-Methoxyacrylates; synthesis of new types of strobilurin fungicides with extended side chains , 1999 .

[25]  T. A. Link,et al.  Complete structure of the 11-subunit bovine mitochondrial cytochrome bc1 complex. , 1998, Science.

[26]  R. Schmidt,et al.  Direct anomeric O-arylation and O-hetarylation of glucose - electron deficient aromatic and hetaromatic compounds in aryl and hetaryl glycoside synthesis , 1995 .

[27]  J. Clough,et al.  Fungicidal β‐methoxyacrylates: From natural products to novel synthetic agricultural fungicides , 1991 .

[28]  G. von Jagow,et al.  Oudemansin, strobilurin A, strobilurin B and myxothiazol: new inhibitors of the bc 1 segment of the respiratory chain with an E‐β‐methoxyacrylate system as common structural element , 1981, FEBS letters.

[29]  T. Anke,et al.  The strobilurins--new antifungal antibiotics from the basidiomycete Strobilurus tenacellus. , 1977, The Journal of antibiotics.