Synthesis And Insecticidal Activity Of4α-Arylsulfonyloxybenzyloxy-2β-Chlor Opodophyllotoxin Derivatives

In continuation of our program aimed at the discovery and development of naturalproducts-based insecticidal agents,14novel4α-arylsulfonyloxybenzyloxy-2β-chloropodophyllotoxin derivatives were stereoselectivelysemisynthesized, and preliminarily evaluated their insecticidal activity against thepre-third-instar larvae of Mythimna separata Walker in vivo.1. Firstly,2β-chloropodophyllotoxin （8） was synthesized from podophyllotoxin as thelead-compound. Meanwhile, arylsulfonyloxybenzaldehyde derivatives （4） were readilyafforded by reaction of o-hydroxybenzaldehyde or p-hydroxybenzaldehyde with arylsulfonylchlorides. Then reduction of4gave aryl-sulfonyloxybenzyl alcohols （5）. Finally,14novel4α-arylsulfonyloxybenzyloxy-2β-chloropodophyllotoxins （9a–g and9a′–g′） werestereoselectively obtained by reaction of8with5in the presence of BF₃·Et₂O. The structuresof all target compounds were well characterized by¹H NMR, HRMS, optical rotation, m.p.,and MS. In order to obtain precise three-dimensional structural information and absoluteconfiguration of9a–g and9a′–g′, the single-crystal structure of9f′was further confirmed byX-ray crystallography.2. The insecticidal activity of9a–g and9a′–g′against the pre-third-instar larvae ofMythimna separata Walker in vivo was screened by the leaf-dipping method at theconcentration of1mg/mL. Five4α-arylsulfonyloxybenzyloxy-2β-chloropodophyllotoxinderivatives showed more promising insecticidal activity than toosendanin at1mg/mL,especially compounds9c′and9g′exhibited the most pronounced insecticidal activity.3. Structure-activity relationship preliminarily demonstrated that arylsulfonyloxy groups atthe C-2position of benzyloxy moiety and the length of the side chain on thebenzenesulfonyloxy group of4α-arylsulfonyloxybenzyloxy-2β-chloropodophyllotoxins mightbe important for the insecticidal activity.