Chinese Journal of Organic Chemistry >
A Feasible Route to Access the ABD Skeleton in Azadirachtin-Type Limonoids
Received date: 2022-04-18
Revised date: 2022-05-31
Online published: 2022-06-17
Supported by
National Key Research and Development Program of China(2017YFD0201404); National Natural Science Foundation of China(21772097); National Natural Science Foundation of China(21572104)
In an effort to rapidly construct the azadirachtin-type limonoids and analogues, a highly diastereoselective synthesis of the ABD tricyclic core in azadirachtin-type limonoids from (–)-carvone has been developed. The synthetic avenue features an intramolecular nitrile oxide-alkene cycloaddition (INOC) reaction to assemble the trans-decalin system in highly stereoselective manner. By further utilizing an efficient sequence of Sonogashira coupling, isoxazoline reduction, stereocontrolled dihydroxylation, mesylation and intramolecular SN2 substitution, a scalable stereoselective synthesis of the tricyclic core skeleton of azadirachtin in 13 linear steps was achieved with 6.1% total yield. This intermediate can serve as a highly functionalized left-wing fragment for the synthesis of azadirachtin and its analogues. Compared with existing methods, the methods reported herein are simple, reliable, easy to implement, and significantly advances research on the synthesis of the azadirachtin-type limonoids.
Changming Dong , Yi Xie , Guangxin Liang . A Feasible Route to Access the ABD Skeleton in Azadirachtin-Type Limonoids[J]. Chinese Journal of Organic Chemistry, 2022 , 42(9) : 2857 -2866 . DOI: 10.6023/cjoc202204048
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