Regioselective syntheses and analyses of phlorofucofuroeckol‐A derivatives

Phlorofucofuroeckol‐A (PFF‐A) is a phlorotannin extracted from various brown algae. PFF‐A shows low toxicity when ingested and various biochemical effects, including antioxidant, anti‐inflammatory, anti‐cancer, and anti‐allergy properties. In this study, various di‐O‐substituted PFF‐A derivatives were synthesized by introducing alkyl or acyl groups at two specific hydroxyls out of the nine nearly equivalent phenolic OH groups present in PFF‐A. The exact molecular structures of the synthesized derivatives were analyzed using two‐dimensional nuclear magnetic resonance (2D NMR) spectroscopy, which confirmed that the substituents were regioselectively introduced at the 1OH and 6OH positions. Small amounts of three mono‐O‐substituted derivatives were generated as by‐products in this reaction, and their structures and regioselectivity were determined using 2D NMR spectroscopy. This study can provide insights into understanding the mechanism of action of eckol‐based compounds and developing new drug candidates. Phlorofucofuroeckol‐A (PFF‐A), a polyphenol extracted from brown algae, has attracted considerable attention owing to its various pharmacological activities. Herein, four 1,6‐disubstituted and three 6‐monosubstituted PFF‐A derivatives were prepared using highly regioselective substitution reactions developed for methyl, benzyl, acetyl, and benzoyl groups. The structures of all derivatives were characterized using 2D NMR techniques, including nuclear Overhauser effect spectroscopy (NOESY), heteronuclear single‐quantum correlation spectroscopy (HSQC), and heteronuclear multiple‐bond correlation spectroscopy (HMBC) NMR.