Synthesis And Insecticidal Activities Of 4α-acyloxy/alkoxyl 2-chloropodophyllotoxin

Podophyllotoxin, besides its use as the lead-compound for the preparation of potent anticancer drugs, also exhibited the interesting insecticidal activity. According to the previous research, it was found that the trans-lactone and 4′-OCH3 moieties of podophyllotoxin were essential to maintain the insecticidal activity. Meanwhile, 2-chloropodophyllotoxin had significant anticancer activity. Based upon the above results, we have synthesized 2-chloropodophyllotoxin derivatives being the trans-lactone and 4′-OCH3 fragments, and the insecticidal activity was screened.1. Podophyllotoxin is used as the lead-compound. Though some typical reactions, we afford 2-chloropodophyllotoxin. 21 novel 4α-acyloxy-2-chloropodophyllotoxin derivatives were semisynthesized by two methods: DIC/DMAP and BF₃·Et₂O. Then, 16 novel 4α-alkyloxy-2-chloropodophyllotoxin derivatives were semisynthesized by using BF₃·Et₂O, which are similar to 4-O-tetrahydropyranyl-2-chloropodophyllotoxin. The structures of these compounds were well characterized by 1H NMR, IR, MS, HRMS, mp and optical ratation. In order to obtain precise three-dimensional structural information and absolute configuration, the single-crystal structures of three compounds were determined by X-ray crystallography.2. 21 novel 4α-acyloxy-2-chloropodophyllotoxin derivatives which were semisynthesized by two methods (DIC/DMAP and BF₃·Et₂O) are the same configuration. Compared with using DIC/DMAP, compounds which were used with BF₃·Et₂O are easier to separate and purify. And we also could get highly purity.3. The insecticidal activity of 4α-acyloxy-2-chloropodophyllotoxin derivatives and 4α-alkoxyl-2-chloropodophyllotoxin derivatives against the pre-third-instar larvae of Mythimna separata Walker was screened by the leaf-dipping method. Among all the tested compounds, especially five 4α-acyloxy-2-chloropodophyllotoxin derivatives, and five 4α-alkoxyl-2-chloropodophyllotoxin derivatives showed more promising and pronounced insecticidal activity than toosendanin, a commercial insecticide.4. Through a comparative study on the relationship between the chemical structures and the insecticidal activity, some interesting results were found as follows: (1) When some substituents were introduced on the C-4 position of 2-chloropodophyllotoxin, the corresponding compounds usually showed more potent insecticidal activity than the podophyllotoxin ones. (2) The length of straight-chain or branched-chain alkyloxy, and heteroatom- containing cycloalkyloxy at the C-4 position of 2-chloropodophyllotoxin were very important for the insecticidal activity.In this study, some compounds had better poisonous activities, which provided some theoretical and experimental basis to seek for highly effective botanical pesticides.