Unexpectedly convenient and stereoselective synthesis of 4α-acyloxy-2-chloropodophyllotoxins in the presence of BF₃ ·Et₂O.

Twenty-one 4α-acyloxy-2-chloropodophyllotoxin derivatives (5a-u), whose C-4 spatial configuration was mainly stereocontrolled by the configuration of C-2 chlorine atom, were unexpectedly prepared by the reaction of 2-chloropodophyllotoxin with carboxylic acids in the presence of BF(3)·Et(2)O. Compared with ordinary esterifications of carboxylic acids mediated by the condensation agent, for example, N,N'-diisopropylcarbodiimide (DIC), the present method made the procedure for the preparation of 4α-acyloxy-2-chloropodophyllotoxins more convenient, practical and easy. Meanwhile, the insecticidal activity of compounds 5a-u was preliminarily evaluated against the pre-third-instar larvae of Mythimna separata Walker in vivo at the concentration of 1mg/mL.