化学学报 ›› 1982, Vol. 40 ›› Issue (11): 1081-1083. 上一篇    下一篇

通讯

青蒿素类似物的立体专一性合成

许杏祥, 黄大中, 朱杰, 周维善   

  1. 中国科学院上海有机化学研究所
  • 投稿日期:1982-04-01 发布日期:2013-06-03
  • 通讯作者: 许杏祥

THE STEREO-CONTROLLED SYNTHESIS OF ARTEANNUIN ANALOG

XU XING-XIANG, HUANG DA-ZHONG, ZHU JIE, ZHOU WEI-SHAN   

  1. Shanghai Institute of Organic Chemistry, Academia Sinica
  • Received:1982-04-01 Published:2013-06-03

青蒿素(1)是从青蒿中分离到的一个具有独特结构的抗疟新药.它的结构包含一个C—O—O—C基团并连接着C—O—C—O—C的交替排列,这种特殊的结构可能与其抗疟活性有关.我们曾用青蒿酸(2)进行光敏氧化,经由⊿5-烯-4-氢过氧化物3合成了天然青蒿素B(4)[1].因而若从5得3的双氢化合物6,再经臭氧化和内分子缩酮反应,似可在C4和C6位之间架一个过氧桥,从而得到一个类似青蒿素结构的化合物.根据这一设想,我们已成功地合成了这个化合物.具有这种独特结构的过氧化物还是首次被合成.

Arteannuin (1) was a new sesduiterpenoid containing a, peroxide linkage and ie the antimalarial principle isolated from Artemisia amnua L.The present investigation deals with the synthesis of its analog 8, which contained tho peroxide moiety in the molecule, starting from arteannuinic acid (2) through photo-oxidation. The key intermediate 5 was obtained from 2 via esterifioation, selective NaBH4 reduction and alkaline hydrolysis. Irradiation of a dilute pyridine elution of 6 in the presence of oxygen and a sensitizer (hematoporphyrin) with 200W high pressure mercury lamp gave the a-hydroperoxide 6. Ozonolysis of 6 in diohloromethane-pyridine afforded the aoetal 7. Activation of the carboxyl group in 7 with TsCl-Et3N resulted in the cyolization of the lactone ring, to afford the final product, arteannuin analog 8.