目的 對(duì)甘草次酸C3、C11、C30進(jìn)行結(jié)構(gòu)改造及其體外抗腫瘤活性研究。方法 甘草次酸經(jīng)鋅汞齊還原為11-脫氧甘草次酸，然后C30-羧基與鹵代烴發(fā)生酯化反應(yīng)，C3-羥基與甲基磺酰氯在0 ℃冰浴條件下發(fā)生甲基磺?；磻?yīng)，最后在104 ℃回流條件下與疊氮鈉發(fā)生消除反應(yīng)，從而得到目標(biāo)產(chǎn)物；通過SRB法對(duì)上述合成的甘草次酸衍生物進(jìn)行體外抗腫瘤活性研究。結(jié)果 設(shè)計(jì)并合成了7個(gè)目標(biāo)產(chǎn)物5a～5g，利用IR、MS和1H-NMR確證了結(jié)構(gòu)；抗腫瘤活性篩選結(jié)果表明5a對(duì)MCF-7的抑制率比母體顯著提高，5a、5c、5e對(duì)A549的抑制率均比母體有所提高。結(jié)論 結(jié)構(gòu)改造合理，對(duì)進(jìn)一步開展甘草次酸衍生物的結(jié)構(gòu)改造和抗腫瘤活性研究具有一定的參考價(jià)值。

Objective To modify the structures of glycyrrhetinic acid C3, C11, and C30 and to study their antitumor activities in vitro. Methods Glycyrrhetinic acid was reduced to 11-deoxy-glycyrrhetinic acid by Zn-Hg. Then the carboxyl group at C30 reacted with halogenated hydrocarbons via esterification reaction, and the hydroxyl group at C3 reacted with methyl sufonyl chloride via methyl sulfonic acid reaction at 0 ℃. The target product was obtained after the elimination reaction with sodium azide at 104 ℃. The antitumor activities of the compounds were tested by SRB assay. Results Seven target products 5a－5g were synthesized, and were characterized by IR, MS and 1H-NMR. The antitumor activity screening results showed that compound 5a exhibited higher inhibitory rate against MCF-7 cells than glycyrrhetinic acid, and compounds 5a－5g all exhibited higher inhibitory rates against A549 cells than glycyrrhetinic acid. Conclusion The structure modification of glycyrrhetinic acid is reasonable, and provids some practical reference value for the further development on the structure modification of glycyrrhetinic acid derivatives and study on anti-tumor activity.

國家自然科學(xué)基金資助項(xiàng)目（21372156）