Total Synthesis of (-)-Qinghaosu IV (Artemisinin D, Arteannuin D)

Abstract

A b s t r a c t -Starting from (-)-p-pinene (3), a total synthesis of (-)-qinghaosu IV (1 ) has been accomplished.(-)-Qinghaosu IV (1 ) (also known as artemisinin D and arteannuin D) is a highly oxygenated sesquiterpene of the cadinane family.This natural alcohol was first isolated in 1982 by Liang and coworkers2 from the Chinese medicinal plant qinghao (Artemisia annual L.), which also produces a large number of cadinane-type terpenoids including (+)-qinghaosu (2),3 a structural isomer o f 1 which is responsible for the antimalarial activity o f the herb.Qinghaosu IV (1 ) was identified as a key metabolite in the microbial metabolism studies carried out by Hufford e t al.4 and could serve as a marker in the investigation of the metabolic pathway of (+)qinghaosu (2) in humans.Recently, we reported an efficient total synthesis of qinghaosu (2) starting from (-)-p-pinene (3).5In the synthesis, P-pinene (3) was converted t o enone ester (4),6 from which the key intermediate ( 5) was prepared via a Diels-Alder process5