The Design, Synthesis, and Evaluation of 1,5,7‐Trisubstituted‐3‐Pyridyl‐Xanthones for Use as Insecticides Starting from Pyripyropene A

Abstract

A readily accessible template of 1,5,7-trisubstituted-3-pyridyl-xanthones was designed starting from naturally occurring pyripyropene A for agrichemical development. Our originally developed Ag CO -mediated oxidative cyclization enabled ready access to the key scaffold, 1,5,7-trihydroxy-3-chloro-xanthone. The chemo- and regioselective sequential introduction of four substituents to the scaffold rapidly afforded the desired, structurally diverse 1,5,7-trisubstituted-3-pyridyl-xanthones. An evaluation of insecticidal activity revealed that one of the synthesized compounds retained insecticidal activity against vetch aphid and green peach aphid. The observed insecticidal spectrum was similar to that of pyripyropene A. The developed template could be a valuable aid for future agrichemical development.

Studies on the Chemical Diversities of Secondary Metabolites Produced by Neosartorya fischeri via the OSMAC Method

“…The in vivo efficacy of pyripyropene A ( 4 ) has also been proved [ 37 ]. Recently, pyripyropene A ( 4 ) has also gained attention as a promising lead for developing insecticides since it exhibited excellent insecticidal activity against aphids by both foliar application and soil drenching without serious toxicological issues [ 15 , 38 , 39 ]. Compounds 1 and 2 were previously prepared by chemical deacetylation of pyripyropene A ( 4 ) [ 40 , 41 ] and used as starting materials in preparing pyripyropene derivatives.…”

Recent advances in the synthesis of xanthones and azaxanthones

“…Despite not being used as often as the basecatalysed intramolecular nucleophilic aromatic substitution, methodologies based on the oxidative cyclization of the benzophenone are also employed for the synthesis of xanthone derivatives. Studies on the cyclization of the readily available model substrate 2,3′,5-trihydroxy benzophenone 28 revealed that the combination of Ag 2 CO 3 and CH 3 CN, at 100°C for 2 h gave the best results towards the cyclization product, with the hydroxyl group being crucial for cyclization that occurs via a single-electron transfer mechanism 144 (Scheme 7C). To obtain 1,5,7-trisubstituted-3-pyridylxanthones with potential as insecticides, the target precursor 1,5,7-trihydroxy-3-chloroxanthone was cyclized using the optimized reaction conditions, in the route for the synthesis of several 1,5,7-trisubstituted-3-pyridylxanthones.…”

O-Annulation Leading to Five-, Six-, and Seven-Membered Cyclic Diaryl Ethers Involving C–H Cleavage

“…In some case, enzymatic oxidation, 60 using Horse Radish Peroxidase Laccase or even microorganism as R. Buffonii, 55 has been used as well. In the case of silver salts, 62 Fuse et al suggested a radical mechanism for the formation of 1,7-dihydroxyxanthone 69. In the proposition, a single electron transfer (SET) to form xanthone ring 67 occurs, generating a radical intermediate stabilised by the 3-hydroxyl group.…”

“…Scheme 17 Proposed radical mechanism for the formation of 1,7-dihydroxyxanthone 62 Recently, Suzuki et al 63 developed the total synthesis of Atroviridin using MnO 2 as oxidant to form the xanthone core. In their case, the proposed mechanism relies on the formation of p-quinone 71 followed by a 1,4-addition of the free hydroxyl group leading to keto-tautomer intermediates 72 and 73, which are demethylated to yield Atroviridin (Scheme 18).…”