光甘草定的全合成研究

Total synthesis study of glabridin

光甘草定是光果甘草中一种特有的异黄酮成分,具有广泛的生物活性。以便宜易得的7-羟基香豆素为原料,与2-甲基-3-丁炔-1-氯反应构建酚炔醚,在酚炔醚的α,β-不饱和内酯部分引α-溴原子得到溴代物酚炔醚,该化合物的炔醚部分在加热条件下,经分子内环化生成关环产物,关环产物与2,4-二甲氧基苯硼酸经Suzuki偶联,还原共轭双键得双羟基化合物、Mitsunobu成醚、脱除甲基,七步以20%的总收率合成了光甘草定,该方法具有原料便宜易得、总路线短、总收率高等优点。

Glabridin is one of the unique isoflavones in Glycyrrhiza glabra and has a broad biological activities.By using commercially available 7-hydroxycoumarin as raw material,phenol alkyl ether was constructed by reacting with 2-methyl-3-butyn-1-chlorine,a bromine atom was introduced into the position of theα,β-unsaturated lactone to afford brominated phenolic alkynyl ether.The alkyne part of the compound was synthesized in seven steps with a total yield of 20%by intramolecular cyclization,and the ring-closing product was coupled with 2,4-dimethoxy⁃phenylboronic acid by Suzuki,and the conjugated double bond was reduced to obtain a dihydroxyl compound,Mit⁃sunobu ether formation,and methyl removal was synthesized in seven steps with a total yield of 20%,which has the advantages of cheap and easy to obtain raw materials,short total route and high total yield.