青蒿素及其一类物的结构和合成 XXI.青蒿酸的全合成  

Studies on Structure and Synthesis of Arteannuin and Related Compounds——XXI. Total Synthesis of Arteannuinic Acid

作　　者：周维善[1] 黄大中[1] 平学凡 张联[1] 朱杰[1] 许杏祥[1] 

机构地区：[1]中国科学院上海有机化学研究所

出　　处：《化学学报》1989年第7期710-715,共6页Acta Chimica Sinica

摘　　要：青蒿酸（1）与抗疟新药青蒿素（2）共存于植物青蒿中，具有显著的抗菌活性，它的结构和立体化学已经确定，并被用作合成青蒿素及其一类物的原料，本文报道了以R－（＋）－香草醛（3）为原料合成1。Arteannuin D (3) coexists with arteannuin (1), which in an antimalarial principle isolated from Chinese medicinal herb Artemisia annua L. In this paper the regioselective synthesis of 3 is reported. The aldehyde-ketone 8 obtained from arteannuinic acid (7), was treated with 1 eq trimethylorthoformate in methanol in the presence of a catalytic amount of p-TsOH to provide 9 and 10 in 86% yield in the ratio of 1 to 1, and with 2 eq. of the orthoformate under the same condition to give only 9 in 88% yield. However, pyrolysis of 9 in xylene did not give the desired intermediate 5, but gave 11 and 12 in the yields of 34% and 30%, respectively. Another approach to the synthesis of 3 is to use enol-silyl ether 13 obtained from 8 as a key intermediate through the following sequence of reactions: 8→10→12→13 in 28% overall yield. Trimethylsilyl enol ether 13 was hydroxylated with N-methyl morpholine N-oxide (NMMNO) and a catalytic amount of OsO_4 to give the 3-OH product 14 regioselectively in 52% yield. While the compound 12 was hydroxylated with OsO_4 and NMMNO, followed by cyolization with 10% K_2CO_3 to produce deoxyarteannuin (2) in 72% yield. After protection of 3-OH of 14 by acetylation, it was hydroxylated with a stoichiometric amount of Os0_4 followed by cyclization with 10% K_2CO_3 to give a mixture of 3 and its 3-OH epimer 15 in 59% yield, which after column chromatography gave 3, m. p. 190--192℃, whose spectroscopic data were identical with those reported in the literature.

关 键 词：青蒿酸 青蒿素 结构 合成 抗疟药物 

分 类 号：TQ463.3[化学工程—制药化工]