Planta Med 2013; 79 - PN102
DOI: 10.1055/s-0033-1352444

A novel chemical synthesis of biflavonoid Rhodophyscin

C Si 1, G Yu 2, L Wu 2, S Liu 2, X Ren 2
  • 1a. Tianjin Key Lab of Pulp & Paper, Tianjin University of Science &Technology, Tianjin 300457, China; b. Jiangsu Provincial Key Lab of Pulp & Paper Science & Technology, Nanjing Forestry University, Nanjing, Jiangsu Province, 210037, China
  • 2Tianjin Key Lab of Pulp & Paper, College of Materials Science & Chemical Engineering, Tianjin University of Science &Technology, Tianjin 300457, China

Rhodophyscin is a biflavanoid ubiquitously occuring in plants, and recently we isolated it from trees of Eucommia, Paulownia, and Juglans. It has been reported that rhodophyscin exhibit various bioactivities including antiinflammatory, antioxidant, neuroprotective, antitumor, antibacterial and antiviral properties [1]. We introduced an efficient synthetic method to achieve rhodophyscin in large scale. Briefly, p-anisaldehyde was iodinated at the 3-position to give 3'-iodo-4-methoxybenzaldehyde (1). Compound 1 was condensed with 2-hydroxy-4,6-dimethoxyacetophenone to forward 4,4',6'-trimethoxy-3-iodo-2'-hydroxychalcone (2). Compound 2 underwent a ring cyclization reaction to produce 4',5,7-trimethoxy-3'-iodoflavone (3). The iodine moiety in 3 was converted to the pinacol functionality to form 4',5,7-trimethoxy-3'-pinacolatoboronflavone (4). Meanwhile, 2',4',6'-trihydroxy-acetophenone (5) was first methylated at the 2 and 4 position to produce 2-hydroxy-4,6-dimethoxyacetophenone (6). Compound 6 was iodinated to forward 2'-hydroxy-3'-iodo-4',6'-dimethoxy-acetophenone (7) which was condensed with p-anisaldehyde to give 4,4',6'-trimethoxy-3'-iodo-2'-hydroxy-chalcone (8). Compound 8 undertook a ring closure reaction to generate 4',5,7-trimethoxy-8-iodoflavone (9). A Suzuki reaction was applied by coupling 4 and 9 to achieve 4',5,7,4''',5'',7''-hexamethoxy-rhodophyscin (10). Finally 10 was subject to demethylation to obtain rhodophyscin. The novel synthesis method can be applied to produce other C-C biflavonoids and biphenyls.

References:

[1] Lin RC. et al. (1994) Planta Med 60: 168 – 170.

Acknowledgements: This work was supported by National Natural Science Foundation of China (31170541, 31000279), Program for New Century Excellent Talents in University (NCET-10 – 0951), Natural Science Foundation of Tianjin City (13JCZDJC), and Foundation (200301) of Jiangsu Provincial Key Laboratory of Pulp and Paper Science and Technology, Nanjing Forestry University, China.