Study On Synthesis And Bioactivity Of Avermectin B1 And Jinggangmycins Derivatives

Avermectin Bl and jinggangmycins are safe and highly effective bio-pesticides with special modes of action. The structural modifications of avermectin Bl were successful in technique and commerce since several derivatives of it had higher bioactivities or extended insecticidal spectrum. Therefore, avermectin Bl and jinggangmycins were selected as lead compounds for the discovery of new pesticides in this dissertation.Firstly, avermectin Bl monosaccharide (2-2) and avermectin Bl aglycone(2-3) were prepared by hydrolysis of avermectin Bl (2-1). The yield of 2-3 wasincreased from 50% to 60.6% by using tetrabutyl ammonium bromide as a phasetransfer catalyst. The heavy emulsification in the separation process was cleared up byextracting with a mixture solvent and washing with aqueous NaCl.5-O-TBDMS-derivatives were prepared from compounds 2-l~2-3 in good yields by optimizing the reaction solvent and the molar ratio of reactants.A facile and effective acylating method of 2-2 and 2-3 by chrysanthemyl chlorides in the presence of DIPEA/DMAP was reported. Thus, six new 13-O-chrysanthemylavermectin B1 aglycones were synthesized in yields of more than 95%; and six new 4'-O-chrysanthemylavermectin Bl monosaccharides were also synthesized in yields of more than 87%.In DMAP/DCC system, four new 4"-Ar-acetylaminoacylavermectin Bl were synthesized in 72-79% yields. The system had such advantages as mild reaction conditions and easy operations.Four jinggangmycins derivatives with different acetyl value were obtained through the control of reaction conditions and the molar ratio of reactants. In four derivatives, the acetyl value of "full- acetyl" jinggangmycins (4-6) was 82.4%, and its maximum absorption wave length was moved from 220 nm to 290 nm, and the solubility was reversed.Five chrysanthemyljinggangamines, one chrysanthemyljinggangmycins and one jinggangamines carbonate were prepared in 22-71% yields. These products were isolated by gel-filteration effectively.The preliminary bioassay of chrysanthemyl derivatives of 2-2 and 2-3 showed that 13-O-chrysanthemyl derivatives of 2-2 exhibited high insecticidal activities and 4'-O-chrysanthemyl derivatives of 2-3 had good insecticidal activities to Spodoptera eridania. It could be found that a free C-5 hydroxyl group was very important for the high bioactivities of above new compounds.The preliminary bioassay of jinggangmycins and jinggangamines derivatives revealed that besides compound 4-6 exhibited low activity to Spodoptera eridania, the other acetylating jinggangmycins derivatives were inactive against the testing pest; surprisingly, many chrysanthemyl derivatives of jinggangmycins and jinggangamines and jinggangamines carbonate showed good activities against the testing pest.In conclusion, the study of this dissertation provides a useful revelation and an effective direction for the further related work.