Synthesis and biological screening of analogues of bioactive acid constituents from the traditional Chinese medicinal plant Liquidambar Formosana

Abstract

Liquidambar formosana (also known as maple) is a tall deciduous tree widely distributed in various regions of the South of the Qinling Mountains and Huaihe River in China, and also found in Northern Vietnam, Laos and South Korea. L. formosana is a famous ornamental plant for leaves are green in spring and summer, and red in autumn. Different plant parts of L. formosana, such as leaf, fruit, bark, and resin, are proved to be treasures as natural medicinal plant resources [1]. Among the bioactive constituents, several diterpenoid acids of the abietane family have been identified. Abietic acid (1) occurs in plants of the genus Abies and is the first member of a class of plant metabolites, the abietane-type diterpenoids. They are characterized by a tricyclic ring system and have shown a wide range of chemical diversity and biological activity.[2,3] Medicinal chemists have studied derivatives of two readily available materials such as dehydroabietic acid (2) and dehydroabietylamine (3, DHAA).[3] To date, there is only one commercial drug, Ecabet® [ecabet sodium (4)], based on abietanes, which is used for the treatment of reflux esophagitis and peptic ulcer disease. Ferruginol (5) exhibits anticancer effects in human ovarian cancer and inhibition of cancer cell migration. Recent studies of sugiol (6) demonstrated in vivo antitumor activity in DU145 prostate xenografts. These biological reports and the simultaneous isolation, (in 2014) by Hua and co-workers, of the new abietane liquiditerpenoic acid A (7), a sugiol analogue, from the resin of Liquidambar formosana [4] and from Pinus massoniana,[5] by Kuo and co-workers named independently as abietopinoic acid, prompted us to synthesize it and study its biological properties along with some analogues. References [1] Ouyang, X. L.; Yi, S.; Lu, H. Y.; Wu, S. M.; Zhao, H. Q. Eur. J. Med. Plants 2016, 17, 1-11. [2] For a review on this topic, see: Gonzalez, M. A. Nat. Prod. Rep. 2015, 32, 684-704. [3] For a review on this topic, see: Gonzalez, M. A. Eur. J. Med. Chem. 2014, 87, 834-842. [4] Shang, H.-J.; Li, D.-Y.; Wang, W.-J.; Li, Z.-L.; Hua, H.-M. Nat. Prod. Res. 2014, 28, 1-6. [5] Mohamed, H. A.; Hsieh, C.-L.; Hsu, C.; Kuo, C.-C.; Kuo, Y.-H. Helv. Chim. Acta 2014, 97, 1146-1151.