Synhesis And Quantitative Structure-Activity Relationships Of Novel 2-Heteroaryl-4-Chromanone Derivatives

Phytoalexins are low molecular weight chemicals that immune system of plants produce and accumulate in response to infection especially of fungal origin. Although their content is not high in plants, yet they have shown uniquely fungicidal activity and played an important role in the plants' defense system, which attracted Chemists and biologists' much attention for a long time. Development of novel pesticides based on phytoalexins has become an attractive new developmental direction. The progress of the phytoalexins isolated from rice is reviewed in this thesis, and flavanane phytoalexins was chosed as lead compound to development novel fungicides. The structure of flavanane phytoalexins was modified in view of bioisosterism and 23 novel title compounds, 2-heteroaryl-4-chromanones, were designed and synthesized, whose structures are confirmed by 'HNMR MS and elemental analyses. The skeletal structures of the title compounds can be shown as following:Prelimilary bioassay indicated that they all show fairly good fungicidal activities against rice blast disease. Based on these results their ICso in vitro were tested and the quantitative relationship between their structures and fungicidal activities was analyzed using comparative molecular field analysis (CoMFA) and Hansch-Fujita approach, the results show that the hydrophobicity is very important for fungicidal activity, and the optimum value for hydrophobicity is C log P = 2.72 (or l癵 K = -0.1179). In addition, other factors such as CMR, f*oi ,.A)i9 are also important for the fungicidal activities. If the molecule is easy to polarize and has small/V value yet high ^019 value, it will show high fungicidal activity. The results of 3D-QSAR analysis suggested that the introduction of small steric bulk but strong electron-releasing group onto the 5> 6^ 7-position of the benzene ring will be favorable to theactivity of the compound .The CoMFA analyses about the electronic property requirement of O7 and Oig were consistent with those derived from the Hansch-Fujita approach. Additionally, we also tested the capacity factor (k') of 15 title compounds using HPLC and established the quantitative structure-retention correlative equation. In the QSAR analyses, we chose l癵 K value as hydrophobic parameter and obtained satisfactory results.