First Concise Total Synthesis of Biologically Interesting Natural Licoagrochalcone B and Its Unnatural Derivatives

Abstract

Pyranochalcones are an abundant subclass of the flavonoid and are widely distributed in nature. Members of the pyranochalcones have been associated with a wide variety of biological activities such as antimutagenic, antimicrobial, anti-ulcer, and antitumor activities and some plants are used in traditional medicines in China and Europe. As part of an ongoing study into traditional medicine and pharmacological tests, the biologically interesting compound, licoagrochalcone B (1) with the pyranochalcone moiety was isolated from Patrinia villosa (BaiJiangCao in China) and Glycyrrhiza glabra (Figure 1). Licoagrochalcone B (1) shows potent anticancer activity against human cancer cell such as A549, BEL-7402, SGC-7901, MCF-7, HT-29, K562, and A 498. Patrinia species are distributed mainly in Central to East Asia and northeast North America. The ShenNongBenCaoJing, a famous ancient Chinese medicinal literary, has documented their use as medicinal plants for more than 2000 years. Some of these plants are still used in traditional medicine as antiviral and antibacterial agents. Licorice, the root and stolon of Glycyrrhiza species, is also one of the oldest and important medicinal plants. It has been shown to have a variety of biological properties such as antimutagenic, anti-ulcer, antitumor, antioxitant, and antimicribial activities. In addition, one of the fractions from the extract of licorice has been developed as an anti-ulcer drug (Aspalon) in Japan. This wide range of biological properties has stimulated interest in the synthesis of naturally occurring licoagrochalcone B (1) and its derivatives 2-7. Recently, we reported the synthesis of natural products of lonchocarpin (12) and its derivative 13 with the pyranochalcone moiety starting from 1,3-cyclohexanedione (8) utilizing ethylenediamine diacetate-catalyzed 2H-pyran formation as a key step (Scheme 1). However, although this lonchocarpin (12) and its derivative 13 contain pyranochalcone structure, they are different from licoagrochalcone B and its derivatives in the chalcone moiety. As an extension of our work to the synthesis of pyranochalcones, we report the first synthesis of a biologically interesting natural compound, licoagrochalcone B (1) along with its derivatives 2-7.